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Chani (character)

Chani ( or  ) is a fictional character featured in Frank Herbert's novels Dune (1965) and Dune Messiah (1969). Known mainly as the Fremen wife and legal concubine of protagonist Paul Atreides, Chani is the daughter of Imperial Planetologist Liet-Kynes and his Fremen wife Faroula, and later the mother of the twins Ghanima and Leto II Atreides. The character is later resurrected as a ghola, appearing in Hunters of Dune (2006) and Sandworms of Dune (2007), Brian Herbert and Kevin J. Anderson's novels which complete the original series.

Chani is portrayed by actress Sean Young in the David Lynch film Dune (1984), and by Barbora Kodetová in the 2000 John Harrison miniseries Frank Herbert's Dune and its 2003 sequel Frank Herbert's Children of Dune. The character is played by Zendaya in the 2021 Denis Villeneuve film Dune and its 2024 sequel.

Dune
In Dune, Paul's prescience begins manifesting itself through dreams while he is still living in his ancestral home on the planet Caladan; he sees Chani in these visions, though they have not yet met. Paul and the Atreides come to the desert planet Arrakis, but Paul's father Duke Leto is soon killed by the Harkonnens and Paul and his mother Lady Jessica are forced to flee into the desert. They are reluctantly taken in by a tribe of the planet's native Fremen, and Chani is the Fremen woman put in charge of protecting and guiding Paul. They soon become lovers, and Paul rises as a religious leader among the Fremen, and is called Muad'Dib.

Already a talented warrior before meeting Paul, Chani becomes deadly after training by Paul and Jessica in the Bene Gesserit martial arts called the "weirding way" by the Fremen. Chani later manages to bring Paul out of the deep spice trance he falls into after using spice essence to enhance his powers. Paul and Chani's first child, Leto II (not to be confused with their later son, Leto II Atreides), is killed as an infant in a Corrino raid on their home in the deep desert.

To cement his control of the Empire after deposing Padishah Emperor Shaddam IV, Paul takes Shaddam's daughter, the Princess Irulan, as his wife. Chani understands the political reasons, but Paul reassures her: "I swear to you now ... that you'll need no title. That woman over there will be my wife and you but a concubine because this is a political thing and we must weld peace out of this moment, enlist the Great Houses of the Landsraad. We must obey the forms. Yet that princess shall have no more of me than my name. No child of mine nor touch nor softness of glance, nor instant of desire."

Jessica adds: "Think on it, Chani: that princess will have the name, yet she'll live as less than a concubine—never to know a moment of tenderness from the man to whom she's bound. While we, Chani, we who carry the name of concubine—history will call us wives."

Dune Messiah
Twelve years later in Dune Messiah, Paul remains completely loyal to Chani. With their breeding program in mind, the Bene Gesserit are desperate to regain control of Paul's bloodline, and are fearful of the effect Chani's "wild" genes may have on their offspring. Wishing to rid himself of their machinations, Paul negotiates with the Bene Gesserit Reverend Mother Gaius Helen Mohiam: "You may have my seed, but not my person ... Irulan banished and inseminated ... You may have my seed for your plans, but no child of Irulan's will sit on my throne." Artificial insemination is prohibited in the wake of the Butlerian Jihad, and the idea of it is as horrific to the Sisterhood as the loss of the "precious Atreides genes".

Irulan, herself Bene Gesserit-trained, secretly feeds Chani contraceptives to prevent her from conceiving an Imperial heir. However, Chani eventually changes to an ancient Fremen diet to enhance fertility; Irulan is unable to interfere, and Chani soon becomes pregnant. Tragically, Chani dies giving birth to the twins Ghanima and Leto II. His intricate plan coming to fruition, the Tleilaxu agent Scytale offers to "resurrect" Chani as a ghola in return for Tleilaxu control of the empire, but Paul has him killed. Through his prescience, Paul can see that Chani's death during childbirth is far less painful and cruel than her possible future fates had she survived.

Children of Dune
Despite her death, Chani lives on as part of the Other Memory of her pre-born twins. In Children of Dune, this ancestral self is summoned by Ghanima for her guidance, but Chani's persona nearly possesses Ghanima completely. Leto II manages to save his sister from this Abomination by summoning Paul through his own Other Memory; Paul threatens Chani, who releases her hold on Ghanima. At the end of the novel, Chani's memory-self becomes a guardian against Ghanima's other ancestral memories who may try to possess her, allowing her daughter's personality to continue and grow in safety.

God Emperor of Dune
According to God Emperor of Dune, a version of Chani's memory-self also exists in Leto II. By the time of the novel, Leto is able to allow his ancestral memories to speak through his mouth without threat of Abomination. At one point, he allows Chani to speak through him.

Hunters of Dune and Sandworms of Dune
In the 2006 Brian Herbert/Kevin J. Anderson sequel Hunters of Dune, gholas of Paul and Chani are among the others created to assist mankind in the climactic battle with what turns out to be the thinking machines.

In Sandworms of Dune (2007), Paul ultimately duels another Paul Atreides ghola — named Paolo — created by the Face Dancers and twisted by the sadistic ghola of Baron Harkonnen himself. Paul is mortally wounded, but the trauma restores his memories and he manages to heal himself. Later, on the recovering planet Dune, the awakened gholas of Paul and Chani go about restoring the planet to its former glory. They have reverted to the ways of the ancient Fremen, resolving to lead simple lives and unafraid of the plots and schemes that had threatened them in their previous lives. Now able to devote all of his attention to her, Chani remarks that Paul has finally learned how to treat his wife. As the novel closes, Paul reaffirms his love for Chani, telling her he has loved her for five thousand years.

In adaptations
Chani is portrayed by actress Sean Young in the David Lynch film Dune (1984),

Barbora Kodetová plays Chani in the John Harrison miniseries Frank Herbert's Dune (2000) and its sequel Frank Herbert's Children of Dune (2003). Emmet Asher-Perrin of Tor.com wrote that "Kodetová is divine as Chani in both her sensitivity and fierceness".

Zendaya portrays Chani in the 2021 Denis Villeneuve film Dune and its 2024 sequel, Dune: Part Two. Zendaya's portrayal of Chani, along with Timothée Chalamet's Paul, were added to Fortnite Battle Royale in October 2021. Villeneuve's depiction of Chani is relatively different from her portrayal in the books: where Herbert wrote her as fiercely loyal to Paul and his cause, in the film Chani is shown to grow increasingly alarmed at Paul's rise in power and doubtful of his proclaimed love for her. When he pledges to marry Princess Irulan and gains the Emperor's power, Chani refuses to bow to him and departs on a sandworm. Villeneuve notes that Dune Messiah was written partly to make clear Herbert's intention that Paul was an anti-hero, with Chani's depiction in the film serving as set-up for Villeneuve's planned Dune Messiah adaptation.

title: Chani (character)


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Talk:Carmen Electra

Name
Tara Patrick got the name Carmen Electra from none other than Prince! — Preceding unsigned comment added by 70.188.234.161 (talk) 06:24, 7 January 2006 (UTC)

Carmen Electra's revived music career
On November 13th, 2012, Carmen released her comeback single "I Like It Loud" featuring Bill Hamel. She recently announced via Twitter that her next single, "Bigger D*ck" will be coming out on May 14th. The page should be updated to reflect this information.

Sources: 1) https://itunes.apple.com/us/album/i-like-it-loud-feat.-bill/id575048308 2) https://twitter.com/carmenelectra/status/330043805988433922 — Preceding unsigned comment added by Gordonabishop (talk • contribs) 14:35, 5 May 2013 (UTC)

Semi-protected edit request on 9 July 2024
In the Personal Life section, it says:

"In February 2024, Electra's petition to change her legal name, Tara Leigh Patrick, into her stage name was granted by a Los Angeles Superior Court."

This wording can be interpreted in two different ways. Carmen Electra is now her legal name. The wording above could be read as Tara Leigh Patrick is now her stage name, which would be incorrect. Perhaps the wording can be tweaked to this?

"In February 2024, the Los Angeles Superior Court granted Electra’s petition to legally change her name from Tara Leigh Patrick to Carmen Electra." 47.28.96.5 (talk) 04:48, 9 July 2024 (UTC)

✅ PianoDan (talk) 17:45, 9 July 2024 (UTC)

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: Talk:Carmen Electra


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Whitehouse.com

whitehouse.com is a political entertainment website that first came online in May 1996. According to a statement on the web, it was originally created by Ransom Scott as a known place where uncensored discussion of government policies could occur before adult content was added to make it more profitable. In June 2022, adult content was added back to the website.

Controversy
The site's hosting of adult content paralleled the dot-com bubble, when Internet development focused on the promotion of websites with .com domains. A person seeking information about the White House, the American landmark residence/place-of-work, might expect to find such a thing at a .com address. The possibility of a minor making this mistake was especially noted. Because of the explicit and commercial content of the site, it was frequently cited as one of the most egregious examples of domain name misuse, up until the domain was sold.

The website whitehouse.org, a humor site that formerly satirized the former U.S. president George W. Bush, remains controversial for similar reasons, although less so because its content is usually much less explicit.

In 2006, PC World ranked Whitehouse.com #13 on its list of "The 25 Worst Web Sites".

Opposition
In December 1997, a cease and desist letter arrived from the White House, stating: "…we do not challenge your right to pursue it or to exercise your First Amendment rights, but we do challenge your right to use the White House, the President, and the First Lady as a marketing device. For adult internet users, that device is, at the least, part of a deceptive scheme. For younger Internet users, it has more disturbing consequences." The letter had no effect and the site stayed up.

Statuses and uses
In 2004, Dan Parisi decided to sell the domain, primarily because his son would be going into kindergarten the next year. The sale did not occur. As of 2003, Parisi was making US$1 million annually from the site alone. Parisi had said he did not want to sell the domain name to anyone in the adult entertainment industry, and even claimed to have turned down what was essentially a blank check from a buyer hiding his identity behind his broker.

In November 2005, the domain appeared to be used for a real estate site. In December 2005 it contained only Google ads, with a notice that a site for investigating people by checking their public records would be coming. In March 2006, whitehouse.com called itself "America's Free Speech Forum". It advertised a cartoon contest and presented links to Associated Press political news stories. In July 2006, the site was a real estate site again, and forwarded to www.house.com. As of November 2006, the site was a search engine for people, which searched over 90 million White Pages listings and 14 million Yellow Pages listings. As of June–October 2007, the site had once again changed and now claimed to be "your source for up-to-date information to help you keep track of the major party candidates for President."

Until early 2009, the domain redirected to the previous real estate website again. The site was being used for home loan modification and debt consolidation, with the disclaimer reading that is not "affiliated or endorsed by the U.S. Government". As of September 2009, the site was a local New Jersey-centered video hosting site. The site's main purpose was to host videos of local town hall meetings in New Jersey.

As of July 2010, the site was a blank page with large black letters stating, "Future site of WhiteHouse.com" with no other information or link. As of Sept 2010, the site returned with the Banner Heading of WhiteHouseLawyers.com. The site's purported main purpose was to provide a search portal for personal injury / disability lawyers based on users location. But upon testing user input including name, phone, state, and e-mail, no listing of lawyers was provided. Later that month the site advertised financial aid opportunities. As of June 2011, the site again redirected to www.house.com.

As of October 2015, the domain was parked, displayed a picture of the White House and text advertisement 'search results' relating to the White House, Washington D.C. or adult services. As of June 2016, the site displayed a blank page with black letters stating, "WhiteHouse.com Official Site". The subtext read, "Celebrating our 19th Anniversary (1997-2016)" and "World's Most Famous Adult Site coming back Summer 2016".

As of April 2017, the site was once again parked, with similar content as in its October 2015 version. As of August 2017, the site was being used to protest the Trump administration in the wake of the Unite the Right rally. As of November 2017, the site was again a parked domain. By January 2018, the site contained a collection of brief political news stories with the slogan "Where Hate does not Live!". The website claims to be owned and operated by WhiteHouse Network LLC. WHOIS data suggests the domain is administrated by Dan Parisi.

As of May 2020, the site was offering information about the COVID-19 pandemic, plus an opinion poll on the Trump administration's handling of the COVID-19 crisis in the United States. It still listed "WhiteHouse Network LLC" as its owner. A misspelled disclaimer at the footer of the site claims "WhiteHouse Beta is not affiliated or endorsed by U.S. Government"[sic]. As of January 2020, the site offers betting for senate and house election results.

In 2022, the website relaunched as a "Adult & Free Speech Site" with adult content once again. In 2023 it shows polls and urges visitors to bet on certain topics; however, there is no adult content on the website as of the 24th of June, 2023.

Legacy
This type of behavior with trademarks led the United States government to the passage of the Anticybersquatting Consumer Protection Act. The ACPA, however, protects only the registration of trademarks as domain names and would not help the U.S. government with the registration of the names of its offices or agencies.

title: Whitehouse.com


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Ballon d'Or

The Ballon d'Or (lit. 'Golden Ball') is an annual football award presented by French magazine France Football since 1956 to honour the player deemed to have performed the best over the previous season.

Conceived by sports writers Gabriel Hanot and Jacques Ferran, the Ballon d'Or was based exclusively on voting by football journalists up until 2006. Originally, it was awarded only to players from Europe and was widely known as the European Footballer of the Year award. In 1995, the Ballon d'Or was expanded to include all players of any origin that have been active at European clubs. The award became a global prize in 2007 with all professional footballers from around the world being eligible; additionally, coaches and captains of national teams were also given the right to vote, before reverting to just journalists in 2016.

Between 2010 and 2015, in an agreement with FIFA, the award was temporarily merged with the FIFA World Player of the Year, and was known as the FIFA Ballon d'Or. That partnership ended in 2016, and the award reverted to the Ballon d'Or, while FIFA also reverted to its own separate annual award, The Best FIFA Men's Player. In 2022, France Football modified the rules for the Ballon d'Or. The timing was changed so that awards were given not for achievements during a calendar year, but for a football season, and it was also determined that only a single journalist from each country in the top 100 of the FIFA Men's World Ranking would be allowed to vote. UEFA co-organizes the Ballon d'Or gala since 2024, with France Football retaining the voting system and the Ballon d'Or name.

Lionel Messi won the award a record eight times, and he is also the current holder of the Ballon d'Or, having won its most recent edition in 2023. Cristiano Ronaldo won it five times and amassed a record eighteen nominations in his career. Michel Platini, Johan Cruyff and Marco van Basten each won the award three times, while Franz Beckenbauer, Ronaldo, Alfredo Di Stéfano, Kevin Keegan and Karl-Heinz Rummenigge have each won it twice.

Overview
The Ballon d'Or is widely regarded as football's most prestigious and valuable individual award. Nevertheless, critics have occasionally described the award as a "popularity contest", criticizing its voting process, its bias in favour of attacking players, and the idea of systematically singling out an individual in a team sport.

Stanley Matthews of England was the inaugural winner of the Ballon d'Or. Prior to 2007, the award was based exclusively on voting by football journalists and was generally known as the continental European Footballer of the Year award in English language and much international media. Even after 2007, it was usually identified with and referred to by that name because of its origin as a European award, until it was merged with the FIFA World Player of the Year award cementing its new worldwide claim. Liberia's George Weah, the only African recipient, became the first non-European to win the award in 1995, the year that rules of eligibility were changed and the Ballon d'Or was expanded to include all players of any origin, active at European clubs; two years later, Ronaldo of Brazil became the first South American to claim the award, and he is still the youngest winner ever at 21 years and 96 days old. The award became a global prize in 2007 with all professional footballers from clubs around the world being eligible; additionally, coaches and captains of national teams were also given the right to vote, before reverting to just journalists in 2016.

Lionel Messi won the Ballon d'Or a record eight times, while five-time winner Cristiano Ronaldo earned the most nominations with eighteen. Messi is the only player to win the award with three different teams and also the only one to win it while playing outside Europe, as well as being the player with the most podiums, finishing in the top-three a record fourteen times. Three players have won the award three times each: Michel Platini, Johan Cruyff and Marco van Basten. With seven awards each, Dutch, German, Portuguese and French players have won the second most Ballons d'Or, underneath Argentina in first with eight. Players from Germany (1972, 1981) and the Netherlands (1988) occupied the top-three spots in a single year. German (1972) and Italian (1988–1990) clubs achieved the same feat, including two individual years dominated by Milan players (1988, 1989), a unique record until Spanish clubs experienced an unprecedented dominance (2009–2012, 2015, 2016) and Barcelona (2010) became the second club to occupy the top-three. The award shows a bias in favour of attacking players, and, over time, it has gone to a more exclusive set of leagues and clubs. Prior to 1995, ten leagues supplied Ballon d'Or winners, whereas only England, France, Germany, Italy, Spain and the United States have supplied winners since then. Spain's La Liga has the most Ballon d'Or winners overall, with twenty-four wins shared between Barcelona and Real Madrid; with twelve wins each, the two Spanish clubs also lead the overall club ranking for producing the most winners.

Between 2010 and 2015 inclusive, the award was merged with a similar one, the FIFA World Player of the Year award, to create the FIFA Ballon d'Or, which was awarded to the world's best male player before FIFA and France Football decided not to continue the merging agreement. The recipients of the joint FIFA Ballon d'Or are considered as winners by both award organizations. After 2011, UEFA created the UEFA Best Player in Europe Award to maintain the tradition of the original Ballon d'Or of specifically honouring a football player from Europe. In 2020, Groupe Amaury, to which France Football belongs, decided that no award would be given for the year due to the impact of the COVID-19 pandemic on association football. The widespread public opinion is that the 2020 Ballon d'Or should have been awarded to Robert Lewandowski.

France Football modified the rules for the Ballon d'Or in 2022. They changed the timing so that awards were given not for achievements during a calendar year, but for a football season. It was also decided that only a single journalist from each country in the top 100 of the FIFA Men's World Ranking would be allowed to vote. The plebiscite had previously been open to all countries since 2007. This brought the Ballon d'Or into line with the UEFA Men's Player of the Year Award which was slightly less dominated by exclusive leagues and, in particular, Cristiano Ronaldo and Lionel Messi in the 2010s. UEFA co-organizes the Ballon d'Or gala since 2024, with France Football retaining the voting system and the Ballon d'Or name.

Winners
Note: Until 2021, the Ballon d'Or was awarded based on player performance during the calendar year. Since 2022, jurors have been instructed to take into account the previous season.

 * Notes

Wins by player

 * Notes

Ballon d'Or Féminin
First awarded in 2018, the Ballon d'Or Féminin honours the female player deemed to have performed the best over the previous season.

Kopa Trophy
Since 2018 France Football has given out the Kopa Trophy to the best performing player under the age of 21. The award is named after 1958 Ballon d'Or winner Raymond Kopa.

Yashin Trophy
First awarded in 2019, the Yashin Trophy is presented to the best goalkeeper of the year. The award is named after Soviet goalkeeper and 1963 Ballon d'Or winner Lev Yashin.

Gerd Müller Trophy
In 2021, France Football awarded Robert Lewandowski with a Striker of the Year award for scoring the most goals the previous season. Following Gerd Müller's death in 2021, the award was renamed for the 2022 edition to the Gerd Müller Trophy.

Sócrates Award
Starting from 2022, France Football gives out the Sócrates Award, which acknowledges footballers for their humanitarian work. The award is named after late Brazilian footballer Sócrates, who co-founded the Corinthians Democracy movement, in opposition to the ruling military dictatorship in Brazil during the 1980s.

Men's Club of the Year
France Football first gave out the Men's Club of the Year award in 2021, with the inaugural winner being Chelsea. Manchester City won back-to-back in 2022 and 2023.

Women's Club of the Year
France Football first gave out the Women's Club of the Year award in 2023, with the inaugural winner being FC Barcelona Femení.

Men's Coach of the Year
France Football is set to give out the Men's Coach of the Year award starting in 2024.

Women's Coach of the Year
France Football is set to give out the Women's Coach of the Year award starting in 2024.

Super Ballon d'Or
An honorary award, under the name Super Ballon d'Or, was awarded to Alfredo Di Stéfano in 1989, who was voted the best multiple-time Ballon d'Or winner ahead of Johan Cruyff and Michel Platini.

In addition Diego Maradona received an honorary Ballon d'Or in 1995 for his services to football dubbed the Golden Ballon d'Or. Pelé also received a similar award during the 2013 FIFA Ballon d'Or ceremony dubbed the FIFA Ballon d'Or Prix d'Honneur.

Football Player of the Century
In 1999, France Football voted Pelé as the Football Player of the Century after consulting their former Ballon d'Or recipients. Among the 34 previous winners, 30 cast their votes, while Stanley Matthews, Omar Sívori and George Best refused to vote, and Lev Yashin had died. Each voter was allotted five votes worth up to five points; however, Di Stéfano only chose a first place, Platini a first and second place, and George Weah two players for fifth place. Pelé was named the greatest by 17 voters, receiving almost double the number of points earned by the second place, Diego Maradona.

Le nouveau palmarès
To coincide with the 60th anniversary of the Ballon d'Or in 2016, France Football published an internationalized reevaluation of the awards presented before 1995, when only European players were eligible to win the award. 12 out of the 39 Ballons d'Or presented during this time period would have been awarded to South American players; in addition to Pelé—seven times—and Diego Maradona—twice—Garrincha, Mario Kempes, and Romário were retrospectively recognized as worthy winners. The original recipients, however, remain unchanged.

Ballon d'Or Dream Team
An all-time all-star team, the Ballon d'Or Dream Team, was published in December 2020 by France Football, honouring football's greatest players of all time. A second and a third team were also published.

title: Ballon d'Or


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Thiruvananthapuram International Airport

Thiruvananthapuram International Airport, is an international airport that serves Thiruvananthapuram, the capital city of Kerala, India. Established in 1932, it is the first airport in the state of Kerala and the fifth international airport of India, officially declared in 1991. It is the operating base of Air India, Air India Express, IndiGo and SpiceJet. The airport, spread over an area of 800 acre, the airport is approximately 3.7 km due west from the city centre and the Padmanabhaswamy Temple, 16 km from Kovalam beach, 13 km from Technopark and 21 km from the under-construction Vizhinjam International Seaport. It shares a visible proximity to Shankumugham Beach making it the nearest airport to the Arabian Sea in India, just about 0.6 miles (approx. 1 km) away from the sea.

The airport is the second-busiest airport in the state of Kerala, eighth-busiest airport in India in terms of international traffic and the 16th overall in India, as of 2024. In the financial year 2023-24, the airport handled over 4.4 million passengers, with a total of over 30,000 aircraft movements. In addition to civil operations, the airport headquarters the Southern Air Command (India) of the Indian Air Force (IAF) and the Indian Coast Guard for their operations. IAF has an exclusive apron to handle all their operations. Thiruvananthapuram Airport also caters to the Rajiv Gandhi Academy for Aviation Technology, which carries out pilot training activities. The airport hosts Air India's narrow body maintenance, repair and overhaul (MRO) unit consisting of twin hangars for servicing Boeing 737-type aircraft, servicing mostly Air India Express aircraft.

History
The airport was established in 1932 as part of the Royal Flying Club under the initiative of Lt. Col. Raja Goda Varman, husband of Karthika Thirunal Lakshmi Bayi, the Rani of Attingal and Travancore Kingdom. Raja Goda Varman, a trained pilot, felt the need for an airport to accommodate Travancore in the aviation map of India and requested the Travancore Durbar to initiate the process of establishing an aerodrome. A detailed report was made and presented to the King by Consort Prince in this regard. It may be mentioned that the King was the brother of Lt. Col. Raja's wife, and the colonel's children were the heirs to the throne.

In 1935, on the royal patronage of Maharaja Chithira Thirunal, Tata Airlines made its maiden flight to the airport using DH.83 Fox Moth aircraft under command of India's first pilot Nevill Vintcent carrying Jamshed Navoroji, a Tata company official, and Kanchi Dwarakadas, commercial agent of Travancore in Karachi, with a special mail from the Viceroy of British India, Lord Willingdon, wishing birthday greetings to the Maharaja.

The first flight took off on 1 November 1935, carrying mails of Royal Anchal (Travancore Post) to Bombay. In 1938, the Royal Government of Travancore acquired a Dakota as the Maharaja's private aircraft and placed the first squadron of the Royal Indian Air Force (Travancore) for protection of the state from aerial attacks. After Independence, the airstrip was used for domestic flights with the construction of a new domestic terminal, Terminal 1.

International operations were initiated by Air India to cities in the Arabian Peninsula in the late 1970s using Boeing 707. By the early 80s, the then-Indian Airlines started service to Colombo, followed by service to Male. Later, Gulf Air, Sri Lankan Airlines (then Air Lanka) and Air Maldives (now Maldivian) started operations. These were followed by Indian Airlines, which started a service to Sharjah. On 1 January 1991, TIA was upgraded to an international airport, making it the fifth international airport of India after Delhi, Bombay, Madras and Calcutta.

On 1 March 2011, the first flight operated from the new international terminal, Terminal 2. IX 536 (Air India Express) from Sharjah marked the first arrival. Air India Express operated the first departure to Dubai from this new terminal. IndianOil Skytanking is the company that introduced single-man refuelling in India and started refuelling operations at Trivandrum in March 2016.

This was the main hub for the defunct Kairali Airlines from 9 January 2013 to 2017.

In November 2018, the Central Government cleared a proposal by the Airports Authority of India (AAI) for leasing out six of its airports, including Trivandrum. The following month, AAI commenced an international competitive bidding process to award Operations, Management and Development (OMD) contracts for the six airports. The Adani Group, GMR Group and Kerala State Industrial Development Corporation (KSIDC) participated in the bidding process that was won by the Adani Group.

Since some public interest litigations were filed concerning the bidding process for the airport, the Union Cabinet gave its approval for awarding the airport to Adani subject to the outcome of Writ Petition. Accordingly, AAI signed a letter of agreement with Adani in September 2020. Adani Thiruvananthapuram International Airport Limited (ATIAL), floated by the Adani Group to run the airport, would operate, manage and develop the airport for fifty years. As per the agreement, ATIAL would get control of the airport only after a concession agreement was executed and the performance bank guarantee was paid and subject to clearance of legal hurdles.

Aippasi and Panguni festival processions
For decades, the airport has been traditionally pausing operations and reschedules flights twice a year to enable religious processions to pass through the airfield. The airport issues a NOTAM (Notice to Airmen) twice yearly before the runway is closed for the bi-annual Aippasi festival, which falls in October-November, and for the Panguni festival, which is held during March-April. The processions used to pass through the same route even before the airport was established in 1932. The temple issues special passes to participants in the 'aarattu' to pass through the airfield's operational areas. The procession is escorted by priests, members of the erstwhile Travancore Royal family, caparisoned elephants, police band and armed and mounted police personnel besides large number of devotees and is a grand spectacle for onlookers.

Runway
Thiruvananthapuram International Airport has a single 3407 m-long runway, equipped to operate any type of aircraft. It has a 1880 m-long parallel taxiway.

Terminal
There are two terminals. Terminal 1 is for domestic flights (except Air India), and Terminal 2 is for all international flights as well as all domestic flights of Air India.

The international terminal ground operations are handled by Air India SATS Airport Services Pvt. Ltd. It is fully air-conditioned with a WiFi facility. The terminal features spacious lounges, natural lighting with extensive use of glass roofing and better conveyance facilities for passengers. It has three baggage carousels and elaborate immigration/customs facilities. Flemingo, India's first privately owned duty-free operator, is managing the duty-free shop at the international terminal.

The domestic terminal has basic amenities including cafés, a beer and wine bar, a book-seller, free local calls, a specialised baby care room and phone-recharging points. Into Plane Services fuelling operations handled by IndianOil Skytanking.

Terminal 1 (Domestic)
The domestic terminal was the first terminal of the airport inaugurated by Chief minister of Kerala EK Nayanar in 1992. It has an area of 9200 m2 and can handle 400 passengers at a time. The terminal has two Aerobridges and two remote gates. All airlines except Air India are served by the domestic terminal.

Terminal 2 (International)
The newly built Terminal 2 has three additional jetways and parking bays to accommodate 8 aircraft. The terminal is built opposite to the current terminal across the runway and is closer to the city side. The terminal, constructed by the AAI and designed by the UK firm, Pascall+Watson Architects, is expected to provide impetus to the development of the IT sector and the tourism industry in the southern districts of Kerala.

The international terminal covers an area of 35000 m2. It can handle the passengers of three Airbus A340s and one Boeing 747 aircraft simultaneously (roughly 1500 passengers). The annual handling capacity of the terminal will be 1.8 million.

The check-in area has a floor area of 950 m2 and an arrival area of 600 m2. To enable the passengers to check in at any counter, a Common Users Terminal Equipment (CUTE) is installed. X-ray machines are attached to the side of the conveyor belts for faster clearance of baggage.

The entrance to the terminal is from Chacka-Eenchakkal Road. A bridge has been built across the Parvathy Puthanar canal to link the new terminal to the Kazhakuttam-Inchivila NH (National Highway) 47 bypass. The new terminal has a car park area that can accommodate about 600 cars.

There is a pre-paid taxi service counter and foreign exchange (Thomas Cook India) counter in the arrivals area.

Thiruvananthapuram Airport was included in the Ministry of civil aviation strategic plan for 2010–2015 to upgrade as a Category-A airport by developing to aerodrome CODE 4E/4F, constructing a parallel runway with taxiways alongside both runways and so forth.

Air traffic control
The air traffic control (ATC) tower is 18 m tall. There are plans to build a new 50 m tall ATC tower for Thiruvananthapuram Airport near the new international terminal. The airport has a CAT-1 instrument landing system (ILS), DVOR and distance measuring equipment (DME). The airport is also equipped with a Mono-pulse Secondary Surveillance Radar, Air Route Surveillance Radar and an Airport Surveillance Radar that allows approach and area control of the airspace around the airport and nearby air routes.

MRO facility
Thiruvananthapuram International Airport hosts Air India's narrow-body maintenance, repair and overhaul (MRO) unit consisting of twin hangars for servicing Boeing 737 type aircraft, servicing mostly Air India Express aircraft. The Maintenance Repair Overhaul is set up on 6.07 ha of land at a cost of Rs. 110 crores. It was commissioned on 16 December 2011. The maintenance of two aircraft can be simultaneously done at the two hangars present at the MRO. The facility is state-of-the-art with 5,000 ft2 of workshop, 10,000 ft2 apron, electrically operated and vertically moving hangar door system, warehouse and office space. The Maintenance, Repair, and Overhaul (MRO) facility of Air India Charters Limited (AICL) at Thiruvananthapuram International Airport was given permission to carry out the crucial ‘C’ checks of their Boeing 737-800 fleet.

Other operations
In addition to civil operations, Thiruvananthapuram Airport also caters to IAF and Coast Guard for their strategical operations and Airforce NCC Cadets' Trg. IAF have an exclusive apron to handle all their operations. Thiruvananthapuram Airport also caters for Rajiv Gandhi Academy for Aviation Technology. The academy has its own hangar facility at the airport. The hangar facility can accommodate 10 trainer aircraft.

Expansion
In November 2023, the AAI announced that the new terminal building will be built at an area covering 44,000 sq.m., an increase from the original plan of 2018, and that out of 18 acres, 16 acres will be acquired for extending the runway to accommodate larger aircraft and handle more flights by September 2024.

Security
Thiruvananthapuram International Airport is listed among the major airports of India. Its safety and security are handled by the Bureau of Civil Aviation Security through the Central Industrial Security Force#Airport Security (CISF). In the past, airport security was under the control of airport police (under the state government). However, following the hijacking of Indian Airlines Flight 814 in 1999, airport security was handed over to CISF. Thiruvananthapuram Airport also has advanced security equipment including X-RAY Baggage inspection (X-BIS), Explosive Trace Detection System (ETDS) and provision of an In-Line Baggage Screening system; at the NITB, state-of-the-art Closed Circuit Television (CCTV), Flight Information Display System (fids) and Public Address (PA) systems, as well as an Interactive Voice Response System (IVRS) for flight information, are there for passengers' convenience.

The In-Line Baggage Screening system (ILBS) was installed at Terminal 2 on 21 July 2020.


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Flying bomb

A flying bomb is a manned or unmanned aerial vehicle or aircraft carrying a large explosive warhead, a precursor to contemporary cruise missiles. In contrast to a bomber aircraft, which is intended to release bombs and then return to its base for re-use, a flying bomb crashes into its target and is therefore destroyed in its attack.

The term flying bomb is most frequently associated with two specific Second World War weapons, the German V-1 and the Japanese Ohka. The former was unpiloted, as the first known cruise missile ever deployed in combat; the latter carried a pilot on a kamikaze mission.

Historic exemplars
The Sphere of March 13, 1915 published an article on "The Possibilities of an Aerial Torpedo Controlled by Wireless", suggested by a "correspondent to the Sphere" and declared feasible by an "aviation expert".

The first attempt to build a flying bomb (alternatively called an "aerial torpedo" in the Navy) was undertaken by Elmer Sperry for the US Navy in 1916, called the Hewitt-Sperry Automatic Airplane, and was based on a Curtiss N-9 seaplane. This led to a mission-specific Curtiss design, the Curtiss-Sperry Flying Bomb, which was almost completely unsuccessful. The US Army also tried to develop a flying bomb in World War I, the Kettering Bug, but the war ended before the program could mature. The functioning but unsuccessful German Mistel flying bomb was essentially an enormous shaped charge mounted on a repurposed twin-engined medium bomber's airframe (most often a Junkers Ju 88) in place of the cockpit, that was guided by a fighter sitting on top. The fighter first took a course towards the target, then released the Mistel which would continue to its target. The best known example of a flying bomb is the German V-1, many of which targeted London in 1944 during World War II.

Types
Flying bombs may be powered or unpowered, piloted or unpiloted, although unpowered flying bombs such as the United States Navy Bat and German Hagelkorn ("Hailstone") and Fritz X designed during World War II are usually referred to as glide bombs. Flying bombs are analogous to modern cruise missiles such as the jet-powered Tomahawk and rocket-powered Exocet, in that they are equipped with wings to provide lift over a long distance and generally have engines that operate up until impact. This is significantly different from ballistic missiles, which are launched on a ballistic trajectory and do not rely on lift to reach their targets.

title: Flying bomb


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Transcriptional regulation

In molecular biology and genetics, transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA (transcription), thereby orchestrating gene activity. A single gene can be regulated in a range of ways, from altering the number of copies of RNA that are transcribed, to the temporal control of when the gene is transcribed. This control allows the cell or organism to respond to a variety of intra- and extracellular signals and thus mount a response. Some examples of this include producing the mRNA that encode enzymes to adapt to a change in a food source, producing the gene products involved in cell cycle specific activities, and producing the gene products responsible for cellular differentiation in multicellular eukaryotes, as studied in evolutionary developmental biology.

The regulation of transcription is a vital process in all living organisms. It is orchestrated by transcription factors and other proteins working in concert to finely tune the amount of RNA being produced through a variety of mechanisms. Bacteria and eukaryotes have very different strategies of accomplishing control over transcription, but some important features remain conserved between the two. Most importantly is the idea of combinatorial control, which is that any given gene is likely controlled by a specific combination of factors to control transcription. In a hypothetical example, the factors A and B might regulate a distinct set of genes from the combination of factors A and C. This combinatorial nature extends to complexes of far more than two proteins, and allows a very small subset (less than 10%) of the genome to control the transcriptional program of the entire cell.

In bacteria

Much of the early understanding of transcription came from bacteria, although the extent and complexity of transcriptional regulation is greater in eukaryotes. Bacterial transcription is governed by three main sequence elements: While these means of transcriptional regulation also exist in eukaryotes, the transcriptional landscape is significantly more complicated both by the number of proteins involved as well as by the presence of introns and the packaging of DNA into histones.
 * Promoters are elements of DNA that may bind RNA polymerase and other proteins for the successful initiation of transcription directly upstream of the gene.
 * Operators recognize repressor proteins that bind to a stretch of DNA and inhibit the transcription of the gene.
 * Positive control elements that bind to DNA and incite higher levels of transcription.

The transcription of a basic bacterial gene is dependent on the strength of its promoter and the presence of activators or repressors. In the absence of other regulatory elements, a promoter's sequence-based affinity for RNA polymerases varies, which results in the production of different amounts of transcript. The variable affinity of RNA polymerase for different promoter sequences is related to regions of consensus sequence upstream of the transcription start site. The more nucleotides of a promoter that agree with the consensus sequence, the stronger the affinity of the promoter for RNA Polymerase likely is.

In the absence of other regulatory elements, the default state of a bacterial transcript is to be in the “on” configuration, resulting in the production of some amount of transcript. This means that transcriptional regulation in the form of protein repressors and positive control elements can either increase or decrease transcription. Repressors often physically occupy the promoter location, occluding RNA polymerase from binding. Alternatively a repressor and polymerase may bind to the DNA at the same time with a physical interaction between the repressor preventing the opening of the DNA for access to the minus strand for transcription. This strategy of control is distinct from eukaryotic transcription, whose basal state is to be off and where co-factors required for transcription initiation are highly gene dependent.

Sigma factors are specialized bacterial proteins that bind to RNA polymerases and orchestrate transcription initiation. Sigma factors act as mediators of sequence-specific transcription, such that a single sigma factor can be used for transcription of all housekeeping genes or a suite of genes the cell wishes to express in response to some external stimuli such as stress.

In addition to processes that regulate transcription at the stage of initiation, mRNA synthesis is also controlled by the rate of transcription elongation. RNA polymerase pauses occur frequently and are regulated by transcription factors, such as NusG and NusA, transcription-translation coupling, and mRNA secondary structure.

In eukaryotes
The added complexity of generating a eukaryotic cell carries with it an increase in the complexity of transcriptional regulation. Eukaryotes have three RNA polymerases, known as Pol I, Pol II, and Pol III. Each polymerase has specific targets and activities, and is regulated by independent mechanisms. There are a number of additional mechanisms through which polymerase activity can be controlled. These mechanisms can be generally grouped into three main areas: All three of these systems work in concert to integrate signals from the cell and change the transcriptional program accordingly.
 * Control over polymerase access to the gene. This is perhaps the broadest of the three control mechanisms. This includes the functions of histone remodeling enzymes, transcription factors, enhancers and repressors, and many other complexes
 * Productive elongation of the RNA transcript. Once polymerase is bound to a promoter, it requires another set of factors to allow it to escape the promoter complex and begin successfully transcribing RNA.
 * Termination of the polymerase. A number of factors which have been found to control how and when termination occurs, which will dictate the fate of the RNA transcript.

While in prokaryotic systems the basal transcription state can be thought of as nonrestrictive (that is, “on” in the absence of modifying factors), eukaryotes have a restrictive basal state which requires the recruitment of other factors in order to generate RNA transcripts. This difference is largely due to the compaction of the eukaryotic genome by winding DNA around histones to form higher order structures. This compaction makes the gene promoter inaccessible without the assistance of other factors in the nucleus, and thus chromatin structure is a common site of regulation. Similar to the sigma factors in prokaryotes, the general transcription factors (GTFs) are a set of factors in eukaryotes that are required for all transcription events. These factors are responsible for stabilizing binding interactions and opening the DNA helix to allow the RNA polymerase to access the template, but generally lack specificity for different promoter sites. A large part of gene regulation occurs through transcription factors that either recruit or inhibit the binding of the general transcription machinery and/or the polymerase. This can be accomplished through close interactions with core promoter elements, or through the long distance enhancer elements.

Once a polymerase is successfully bound to a DNA template, it often requires the assistance of other proteins in order to leave the stable promoter complex and begin elongating the nascent RNA strand. This process is called promoter escape, and is another step at which regulatory elements can act to accelerate or slow the transcription process. Similarly, protein and nucleic acid factors can associate with the elongation complex and modulate the rate at which the polymerase moves along the DNA template.

At the level of chromatin state
In eukaryotes, genomic DNA is highly compacted in order to be able to fit it into the nucleus. This is accomplished by winding the DNA around protein octamers called histones, which has consequences for the physical accessibility of parts of the genome at any given time. Significant portions are silenced through histone modifications, and thus are inaccessible to the polymerases or their cofactors. The highest level of transcription regulation occurs through the rearrangement of histones in order to expose or sequester genes, because these processes have the ability to render entire regions of a chromosome inaccessible such as what occurs in imprinting.

Histone rearrangement is facilitated by post-translational modifications to the tails of the core histones. A wide variety of modifications can be made by enzymes such as the histone acetyltransferases (HATs),  histone methyltransferases (HMTs), and  histone deacetylases (HDACs), among others. These enzymes can add or remove covalent modifications such as methyl groups, acetyl groups, phosphates, and ubiquitin. Histone modifications serve to recruit other proteins which can either increase the compaction of the chromatin and sequester promoter elements, or to increase the spacing between histones and allow the association of transcription factors or polymerase on open DNA. For example, H3K27 trimethylation by the polycomb complex PRC2 causes chromosomal compaction and gene silencing. These histone modifications may be created by the cell, or inherited in an epigenetic fashion from a parent.

At the level of cytosine methylation

Transcription regulation at about 60% of promoters is controlled by methylation of cytosines within CpG dinucleotides (where 5’ cytosine is followed by 3’ guanine or CpG sites). 5-methylcytosine (5-mC) is a methylated form of the DNA base cytosine (see Figure). 5-mC is an epigenetic marker found predominantly within CpG sites. About 28 million CpG dinucleotides occur in the human genome. In most tissues of mammals, on average, 70% to 80% of CpG cytosines are methylated (forming 5-methylCpG or 5-mCpG). Methylated cytosines within 5’cytosine-guanine 3’ sequences often occur in groups, called CpG islands. About 60% of promoter sequences have a CpG island while only about 6% of enhancer sequences have a CpG island. CpG islands constitute regulatory sequences, since if CpG islands are methylated in the promoter of a gene this can reduce or silence gene transcription.

DNA methylation regulates gene transcription through interaction with methyl binding domain (MBD) proteins, such as MeCP2, MBD1 and MBD2. These MBD proteins bind most strongly to highly methylated CpG islands. These MBD proteins have both a methyl-CpG-binding domain as well as a transcription repression domain. They bind to methylated DNA and guide or direct protein complexes with chromatin remodeling and/or histone modifying activity to methylated CpG islands. MBD proteins generally repress local chromatin such as by catalyzing the introduction of repressive histone marks, or creating an overall repressive chromatin environment through nucleosome remodeling and chromatin reorganization.

Transcription factors are proteins that bind to specific DNA sequences in order to regulate the expression of a gene. The binding sequence for a transcription factor in DNA is usually about 10 or 11 nucleotides long. As summarized in 2009, Vaquerizas et al. indicated there are approximately 1,400 different transcription factors encoded in the human genome by genes that constitute about 6% of all human protein encoding genes. About 94% of transcription factor binding sites (TFBSs) that are associated with signal-responsive genes occur in enhancers while only about 6% of such TFBSs occur in promoters.

EGR1 protein is a particular transcription factor that is important for regulation of methylation of CpG islands. An EGR1 transcription factor binding site is frequently located in enhancer or promoter sequences. There are about 12,000 binding sites for EGR1 in the mammalian genome and about half of EGR1 binding sites are located in promoters and half in enhancers. The binding of EGR1 to its target DNA binding site is insensitive to cytosine methylation in the DNA.

While only small amounts of EGR1 transcription factor protein are detectable in cells that are un-stimulated, translation of the EGR1 gene into protein at one hour after stimulation is drastically elevated. Expression of EGR1 transcription factor proteins, in various types of cells, can be stimulated by growth factors, neurotransmitters, hormones, stress and injury. In the brain, when neurons are activated, EGR1 proteins are up-regulated and they bind to (recruit) the pre-existing TET1 enzymes which are highly expressed in neurons. TET enzymes can catalyse demethylation of 5-methylcytosine. When EGR1 transcription factors bring TET1 enzymes to EGR1 binding sites in promoters, the TET enzymes can demethylate the methylated CpG islands at those promoters. Upon demethylation, these promoters can then initiate transcription of their target genes. Hundreds of genes in neurons are differentially expressed after neuron activation through EGR1 recruitment of TET1 to methylated regulatory sequences in their promoters.

The methylation of promoters is also altered in response to signals. The three mammalian DNA methyltransferasess (DNMT1, DNMT3A, and DNMT3B) catalyze the addition of methyl groups to cytosines in DNA. While DNMT1 is a “maintenance” methyltransferase, DNMT3A and DNMT3B can carry out new methylations. There are also two splice protein isoforms produced from the DNMT3A gene: DNA methyltransferase proteins DNMT3A1 and DNMT3A2.

The splice isoform DNMT3A2 behaves like the product of a classical immediate-early gene and, for instance, it is robustly and transiently produced after neuronal activation. Where the DNA methyltransferase isoform DNMT3A2 binds and adds methyl groups to cytosines appears to be determined by histone post translational modifications.

On the other hand, neural activation causes degradation of DNMT3A1 accompanied by reduced methylation of at least one evaluated targeted promoter.

Transcription factors
Transcription factors are proteins that bind to specific DNA sequences in order to regulate the expression of a given gene. There are approximately 1,400 transcription factors in the human genome and they constitute about 6% of all human protein coding genes. The power of transcription factors resides in their ability to activate and/or repress wide repertoires of downstream target genes. The fact that these transcription factors work in a combinatorial fashion means that only a small subset of an organism's genome encodes transcription factors. Transcription factors function through a wide variety of mechanisms. In one mechanism, CpG methylation influences binding of most transcription factors to DNA—in some cases negatively and in others positively. In addition, often they are at the end of a signal transduction pathway that functions to change something about the factor, like its subcellular localization or its activity. Post-translational modifications to transcription factors located in the cytosol can cause them to translocate to the nucleus where they can interact with their corresponding enhancers. Other transcription factors are already in the nucleus, and are modified to enable the interaction with partner transcription factors. Some post-translational modifications known to regulate the functional state of transcription factors are phosphorylation, acetylation, SUMOylation and ubiquitylation. Transcription factors can be divided in two main categories: activators and repressors. While activators can interact directly or indirectly with the core machinery of transcription through enhancer binding, repressors predominantly recruit co-repressor complexes leading to transcriptional repression by chromatin condensation of enhancer regions. It may also happen that a repressor may function by allosteric competition against a determined activator to repress gene expression: overlapping DNA-binding motifs for both activators and repressors induce a physical competition to occupy the site of binding. If the repressor has a higher affinity for its motif than the activator, transcription would be effectively blocked in the presence of the repressor. Tight regulatory control is achieved by the highly dynamic nature of transcription factors. Again, many different mechanisms exist to control whether a transcription factor is active. These mechanisms include control over protein localization or control over whether the protein can bind DNA. An example of this is the protein HSF1, which remains bound to Hsp70 in the cytosol and is only translocated into the nucleus upon cellular stress such as heat shock. Thus the genes under the control of this transcription factor will remain untranscribed unless the cell is subjected to stress.

Enhancers
Enhancers or cis-regulatory modules/elements (CRM/CRE) are non-coding DNA sequences containing multiple activator and repressor binding sites. Enhancers range from 200 bp to 1 kb in length and can be either proximal, 5’ upstream to the promoter or within the first intron of the regulated gene, or distal, in introns of neighboring genes or intergenic regions far away from the locus. Through DNA looping, active enhancers contact the promoter dependently of the core DNA binding motif promoter specificity. Promoter-enhancer dichotomy provides the basis for the functional interaction between transcription factors and transcriptional core machinery to trigger RNA Pol II escape from the promoter. Whereas one could think that there is a 1:1 enhancer-promoter ratio, studies of the human genome predict that an active promoter interacts with 4 to 5 enhancers. Similarly, enhancers can regulate more than one gene without linkage restriction and are said to “skip” neighboring genes to regulate more distant ones. Even though infrequent, transcriptional regulation can involve elements located in a chromosome different from one where the promoter resides. Proximal enhancers or promoters of neighboring genes can serve as platforms to recruit more distal elements.

Enhancer activation and implementation

Up-regulated expression of genes in mammals can be initiated when signals are transmitted to the promoters associated with the genes. Cis-regulatory DNA sequences that are located in DNA regions distant from the promoters of genes can have very large effects on gene expression, with some genes undergoing up to 100-fold increased expression due to such a cis-regulatory sequence. These cis-regulatory sequences include enhancers, silencers, insulators and tethering elements. Among this constellation of sequences, enhancers and their associated transcription factor proteins have a leading role in the regulation of gene expression.

Enhancers are sequences of the genome that are major gene-regulatory elements. Enhancers control cell-type-specific gene expression programs, most often by looping through long distances to come in physical proximity with the promoters of their target genes. In a study of brain cortical neurons, 24,937 loops were found, bringing enhancers to promoters. Multiple enhancers, each often at tens or hundred of thousands of nucleotides distant from their target genes, loop to their target gene promoters and coordinate with each other to control expression of their common target gene.

The schematic illustration in this section shows an enhancer looping around to come into close physical proximity with the promoter of a target gene. The loop is stabilized by a dimer of a connector protein (e.g. dimer of CTCF or YY1), with one member of the dimer anchored to its binding motif on the enhancer and the other member anchored to its binding motif on the promoter (represented by the red zigzags in the illustration). Several cell function specific transcription factor proteins (in 2018 Lambert et al. indicated there were about 1,600 transcription factors in a human cell ) generally bind to specific motifs on an enhancer and a small combination of these enhancer-bound transcription factors, when brought close to a promoter by a DNA loop, govern the level of transcription of the target gene. Mediator (coactivator) (a complex usually consisting of about 26 proteins in an interacting structure) communicates regulatory signals from enhancer DNA-bound transcription factors directly to the RNA polymerase II (RNAP II) enzyme bound to the promoter.

Enhancers, when active, are generally transcribed from both strands of DNA with RNA polymerases acting in two different directions, producing two eRNAs as illustrated in the Figure. An inactive enhancer may be bound by an inactive transcription factor. Phosphorylation of the transcription factor may activate it and that activated transcription factor may then activate the enhancer to which it is bound (see small red star representing phosphorylation of a transcription factor bound to an enhancer in the illustration). An activated enhancer begins transcription of its RNA before activating a promoter to initiate transcription of messenger RNA from its target gene.

Regulatory landscape
Transcriptional initiation, termination and regulation are mediated by “DNA looping” which brings together promoters, enhancers, transcription factors and RNA processing factors to accurately regulate gene expression. Chromosome conformation capture (3C) and more recently Hi-C techniques provided evidence that active chromatin regions are “compacted” in nuclear domains or bodies where transcriptional regulation is enhanced. The configuration of the genome is essential for enhancer-promoter proximity. Cell-fate decisions are mediated upon highly dynamic genomic reorganizations at interphase to modularly switch on or off entire gene regulatory networks through short to long range chromatin rearrangements. Related studies demonstrate that metazoan genomes are partitioned in structural and functional units around a megabase long called Topological association domains (TADs) containing dozens of genes regulated by hundreds of enhancers distributed within large genomic regions containing only non-coding sequences. The function of TADs is to regroup enhancers and promoters interacting together within a single large functional domain instead of having them spread in different TADs. However, studies of mouse development point out that two adjacent TADs may regulate the same gene cluster. The most relevant study on limb evolution shows that the TAD at the 5’ of the HoxD gene cluster in tetrapod genomes drives its expression in the distal limb bud embryos, giving rise to the hand, while the one located at 3’ side does it in the proximal limb bud, giving rise to the arm. Still, it is not known whether TADs are an adaptive strategy to enhance regulatory interactions or an effect of the constrains on these same interactions. TAD boundaries are often composed by housekeeping genes, tRNAs, other highly expressed sequences and Short Interspersed Elements (SINE). While these genes may take advantage of their border position to be ubiquitously expressed, they are not directly linked with TAD edge formation. The specific molecules identified at boundaries of TADs are called insulators or architectural proteins because they not only block enhancer leaky expression but also ensure an accurate compartmentalization of cis-regulatory inputs to the targeted promoter. These insulators are DNA-binding proteins like CTCF and TFIIIC that help recruiting structural partners such as cohesins and condensins. The localization and binding of architectural proteins to their corresponding binding sites is regulated by post-translational modifications. DNA binding motifs recognized by architectural proteins are either of high occupancy and at around a megabase of each other or of low occupancy and inside TADs. High occupancy sites are usually conserved and static while intra-TADs sites are dynamic according to the state of the cell therefore TADs themselves are compartmentalized in subdomains that can be called subTADs from few kb up to a TAD long (19). When architectural binding sites are at less than 100 kb from each other, Mediator proteins are the architectural proteins cooperate with cohesin. For subTADs larger than 100 kb and TAD boundaries, CTCF is the typical insulator found to interact with cohesion.

Of the pre-initiation complex and promoter escape
In eukaryotes, ribosomal rRNA and the tRNAs involved in translation are controlled by RNA polymerase I (Pol I) and RNA polymerase III (Pol III). RNA Polymerase II (Pol II) is responsible for the production of messenger RNA (mRNA) within the cell. Particularly for Pol II, much of the regulatory checkpoints in the transcription process occur in the assembly and escape of the pre-initiation complex. A gene-specific combination of transcription factors will recruit TFIID and/or TFIIA to the core promoter, followed by the association of TFIIB, creating a stable complex onto which the rest of the General Transcription Factors (GTFs) can assemble. This complex is relatively stable, and can undergo multiple rounds of transcription initiation. After the binding of TFIIB and TFIID, Pol II the rest of the GTFs can assemble. This assembly is marked by the post-translational modification (typically phosphorylation) of the C-terminal domain (CTD) of Pol II through a number of kinases. The CTD is a large, unstructured domain extending from the RbpI subunit of Pol II, and consists of many repeats of the heptad sequence YSPTSPS. TFIIH, the helicase that remains associated with Pol II throughout transcription, also contains a subunit with kinase activity which will phosphorylate the serines 5 in the heptad sequence. Similarly, both CDK8 (a subunit of the massive multiprotein Mediator complex) and CDK9 (a subunit of the p-TEFb elongation factor), have kinase activity towards other residues on the CTD. These phosphorylation events promote the transcription process and serve as sites of recruitment for mRNA processing machinery. All three of these kinases respond to upstream signals, and failure to phosphorylate the CTD can lead to a stalled polymerase at the promoter.

In cancer
In vertebrates, the majority of gene promoters contain a CpG island with numerous CpG sites. When many of a gene's promoter CpG sites are methylated the gene becomes silenced. Colorectal cancers typically have 3 to 6 driver mutations and 33 to 66 hitchhiker or passenger mutations. However, transcriptional silencing may be of more importance than mutation in causing progression to cancer. For example, in colorectal cancers about 600 to 800 genes are transcriptionally silenced by CpG island methylation (see regulation of transcription in cancer). Transcriptional repression in cancer can also occur by other epigenetic mechanisms, such as altered expression of microRNAs. In breast cancer, transcriptional repression of BRCA1 may occur more frequently by over-expressed microRNA-182 than by hypermethylation of the BRCA1 promoter (see Low expression of BRCA1 in breast and ovarian cancers).

title: Transcriptional regulation