Editing TATA box (section)

== Function ==

=== Role in transcription initiation ===
The TATA-box is the site of [[Transcription preinitiation complex|preinitiation complex]] formation, which is the first step in transcription initiation in eukaryotes. Formation of the preinitiation complex begins when the multi-subunit transcription factor II D ([[Transcription factor II D|TFIID]]) binds to the TATA box at its [[TATA-binding protein|TATA-binding protein (TBP)]] subunit.<ref name=":4" /> TBP binds to the [[minor groove]]<ref>{{cite journal | vauthors = Starr DB, Hawley DK | title = TFIID binds in the minor groove of the TATA box | journal = Cell | volume = 67 | issue = 6 | pages = 1231–40 | date = December 1991 | pmid = 1760847 | doi=10.1016/0092-8674(91)90299-e| s2cid = 10297041 }}</ref> of the TATA box via a region of antiparallel [[Beta sheet|β sheets]] in the protein.<ref name=":8"/> Three types of molecular interactions contribute to [[TATA-binding protein|TBP]] binding to the TATA box:
# Four [[phenylalanine]] residues(Phe57, Phe74, Phe148, Phe165) on TBP bind to DNA and form kinks in the DNA, forcing the DNA minor groove open.<ref name=":8">{{cite journal | vauthors = Kim JL, Nikolov DB, Burley SK | title = Co-crystal structure of TBP recognizing the minor groove of a TATA element | journal = Nature | volume = 365 | issue = 6446 | pages = 520–7 | date = October 1993 | pmid = 8413605 | doi = 10.1038/365520a0 | bibcode = 1993Natur.365..520K | s2cid = 4371241 }}</ref><ref name=":9">{{cite journal | vauthors = Nikolov DB, Chen H, Halay ED, Hoffman A, Roeder RG, Burley SK | title = Crystal structure of a human TATA box-binding protein/TATA element complex | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 10 | pages = 4862–7 | date = May 1996 | pmid = 8643494 | doi=10.1073/pnas.93.10.4862 | pmc=39370| bibcode = 1996PNAS...93.4862N | doi-access = free }}</ref><ref name=":10">{{cite journal | vauthors = Kim Y, Geiger JH, Hahn S, Sigler PB | title = Crystal structure of a yeast TBP/TATA-box complex | journal = Nature | volume = 365 | issue = 6446 | pages = 512–20 | date = October 1993 | pmid = 8413604 | doi = 10.1038/365512a0 | bibcode = 1993Natur.365..512K | s2cid = 4336203 }}</ref>
# Four [[hydrogen bond]]s form between polar side chains on TBP [[amino acid]] (Asn27, Asn117, Thr82, Thr173)( and [[Nucleobase|bases]] in the [[minor groove]].<ref name=":8" />
# Numerous [[Hydrophobe|hydrophobic]] interactions(~15) form between TBP residues(notably Ile152 and Leu163) and DNA [[Nucleobase|bases]], including [[Van der Waals force|van der Waals]] forces.<ref name=":8" /><ref name=":9" /><ref name=":10" />
Additionally, binding of [[TATA-binding protein|TBP]] is facilitated by stabilizing interactions with DNA flanking the TATA box, which consists of G-C rich sequences.<ref>{{cite journal | vauthors = Horikoshi M, Bertuccioli C, Takada R, Wang J, Yamamoto T, Roeder RG | title = Transcription factor TFIID induces DNA bending upon binding to the TATA element | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 3 | pages = 1060–4 | date = February 1992 | pmid = 1736286 | doi=10.1073/pnas.89.3.1060 | pmc=48385| bibcode = 1992PNAS...89.1060H | doi-access = free }}</ref> These secondary interactions induce bending of the DNA and helical unwinding.<ref>{{cite journal | vauthors = Blair RH, Goodrich JA, Kugel JF | title = Single-molecule fluorescence resonance energy transfer shows uniformity in TATA binding protein-induced DNA bending and heterogeneity in bending kinetics | journal = Biochemistry | volume = 51 | issue = 38 | pages = 7444–55 | date = September 2012 | pmid = 22934924 | pmc = 3551999 | doi = 10.1021/bi300491j }}</ref> The degree of DNA bending is species and sequence dependent. For example, one study used the adenovirus TATA promoter sequence (5'-CGC'''TATAAAAG'''GGC-3') as a model binding sequence and found that human TBP binding to the TATA box induced a 97° bend toward the [[Nucleic acid double helix|major groove]] while the yeast TBP protein only induced an 82° bend.<ref>{{cite journal | vauthors = Whittington JE, Delgadillo RF, Attebury TJ, Parkhurst LK, Daugherty MA, Parkhurst LJ | title = TATA-binding protein recognition and bending of a consensus promoter are protein species dependent | journal = Biochemistry | volume = 47 | issue = 27 | pages = 7264–73 | date = July 2008 | pmid = 18553934 | doi = 10.1021/bi800139w | s2cid = 7460689 | url = http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1005&context=chemistryparkhurst | url-access = subscription }}</ref> [[X-ray crystallography]] studies of TBP/TATA-box complexes generally agree that the DNA goes through an ~80° bend during the process of TBP-binding.<ref name=":8" /><ref name=":9" /><ref name=":10" />

The conformational changes induced by [[TATA-binding protein|TBP]] binding to the TATA box allows for additional [[transcription factor]]s and [[RNA polymerase II]] to bind to the [[Promoter (genetics)|promoter]] region. TFIID first binds to the TATA box, facilitated by [[TFIIA]] binding to the upstream part of the [[TFIID]] complex.<ref>{{cite journal | vauthors = Louder RK, He Y, López-Blanco JR, Fang J, Chacón P, Nogales E | title = Structure of promoter-bound TFIID and model of human pre-initiation complex assembly | journal = Nature | volume = 531 | issue = 7596 | pages = 604–9 | date = March 2016 | pmid = 27007846 | doi = 10.1038/nature17394 | pmc=4856295| bibcode = 2016Natur.531..604L }}</ref><ref>{{cite journal | vauthors = Wang J, Zhao S, He W, Wei Y, Zhang Y, Pegg H, Shore P, Roberts SG, Deng W | title = A transcription factor IIA-binding site differentially regulates RNA polymerase II-mediated transcription in a promoter context-dependent manner | journal = The Journal of Biological Chemistry | volume = 292 | issue = 28 | pages = 11873–11885 | date = July 2017 | pmid = 28539359 | pmc = 5512080 | doi = 10.1074/jbc.M116.770412 | doi-access = free }}</ref> [[TFIIB]] then binds to the TFIID-[[TFIIA]]-DNA complex through interactions both upstream and downstream of the TATA box.<ref name=":13">{{cite journal | vauthors = Krishnamurthy S, Hampsey M | title = Eukaryotic transcription initiation | journal = Current Biology | volume = 19 | issue = 4 | pages = R153–6 | date = February 2009 | pmid = 19243687 | doi = 10.1016/j.cub.2008.11.052 | doi-access = free }}</ref> [[RNA polymerase II]] is then recruited to this multi-protein complex with the help of [[TFIIF]].<ref name=":13" /> Additional transcription factors then bind, first [[TFIIE]] and then [[TFIIH]].<ref name=":13" /> This completes the assembly of the [[Transcription preinitiation complex|preinitiation complex]] for eukaryotic transcription.<ref name=":4" /> Generally, the TATA box is found at RNA polymerase II promoter regions, although some ''[[in vitro]]'' studies have demonstrated that [[RNA polymerase III]] can recognize TATA sequences.<ref>{{cite journal | vauthors = Duttke SH | title = RNA polymerase III accurately initiates transcription from RNA polymerase II promoters in vitro | journal = The Journal of Biological Chemistry | volume = 289 | issue = 29 | pages = 20396–404 | date = July 2014 | pmid = 24917680 | pmc = 4106352 | doi = 10.1074/jbc.M114.563254 | doi-access = free }}</ref>

This cluster of RNA polymerase II and various transcription factors is known as the basal transcriptional complex (BTC). In this state, it only gives a low level of transcription. Other factors must stimulate the BTC to increase transcription levels.<ref name=":11" /> One such example of a BTC stimulating region of DNA is the [[CAAT box]]. Additional factors, including the [[Mediator (coactivator)|Mediator complex]], transcriptional regulatory proteins, and [[nucleosome]]-modifying [[enzyme]]s also enhance [[Transcription (biology)|transcription]] ''[[in vivo]]''.<ref name=":4" />

=== Interactions ===
In specific cell types or on specific promoters TBP can be replaced by one of several TBP-related factors (TRF1 in [[Drosophila]], TBPL1/TRF2 in [[metazoa]]ns, TBPL2/TRF3 in [[vertebrate]]s), some of which interact with the TATA box similar to [[TATA-binding protein|TBP]].<ref>{{cite journal | vauthors = Akhtar W, Veenstra GJ | title = TBP-related factors: a paradigm of diversity in transcription initiation | journal = Cell & Bioscience | volume = 1 | issue = 1 | pages = 23 | date = 1 January 2011 | pmid = 21711503 | pmc = 3142196 | doi = 10.1186/2045-3701-1-23 | doi-access = free }}</ref> Interaction of TATA boxes with a variety of [[Activator (genetics)|activators]] or [[repressor]]s can influence the [[Transcription (biology)|transcription]] of [[gene]]s in many ways{{Citation needed|date=December 2018}}. [[Enhancer (genetics)|Enhancers]] are long-range regulatory elements that increase promoter activity while [[Silencer (genetics)|silencers]] repress promoter activity.