General transcription factor

In bacteria, transcription initiation requires an RNA polymerase and a single GTF: sigma factor.

File:Preinitiation complex.png

In archaea and eukaryotes, transcription initiation requires an RNA polymerase and a set of multiple GTFs to form a transcription preinitiation complex. Transcription initiation by eukaryotic RNA polymerase II involves the following GTFs:{{cite journal | last1 = Orphanides|first1= George|last2=Lagrange|first2=Thierry|last3=Reinberg|first3= Danny| title = The general transcription factors of RNA polymerase II | journal = Genes & Development | volume = 10 | issue = 21 | pages = 2657–83 | date = November 1996 | pmid = 8946909 | doi = 10.1101/gad.10.21.2657 | doi-access = free }}{{open access}}

• TFIIA – stabilizes the interaction between the TATA box and TFIID/TATA binding protein (TBP)
• TFIIB – recognizes the B recognition element (BRE) in promoters
• TFIID – binds to TBP and recognizes TBP associated factors (TAFs), also adds promoter selectivity
• TFIIE – attracts and regulates TFIIH
• TFIIF – stabilizes RNA polymerase interaction with TBP and TFIIB; helps attract TFIIE and TFIIH
• TFIIH – unwinds DNA at the transcription start point, phosphorylates Ser5 of the RNA polymerase CCTD, releases RNA polymerase from the promoter

{{main|Sigma factor}}

A sigma factor is a protein needed only for initiation of RNA synthesis in bacteria.{{cite journal | last1= Gruber|first1= Tanja M.| last2=Gross|first2= Carol A. | title = Multiple sigma subunits and the partitioning of bacterial transcription space | journal = Annual Review of Microbiology | volume = 57 | pages = 441–66 | date = October 2003 | pmid = 14527287 | doi = 10.1146/annurev.micro.57.030502.090913}} Sigma factors provide promoter recognition specificity to the RNA polymerase (RNAP) and contribute to DNA strand separation, then dissociating from the RNA polymerase core enzyme following transcription initiation.{{cite journal |last1=Borukhov |first1=Sergei |last2=Nudler |first2=Evgeny |title=RNA polymerase holoenzyme: structure, function and biological implications. |journal=Current Opinion in Microbiology |date=April 2003 |volume=6 |issue=2 |pages=93–100 |doi=10.1016/S1369-5274(03)00036-5 |pmid=12732296 |issn=1369-5274}} The RNA polymerase core associates with the sigma factor to form RNA polymerase holoenzyme. Sigma factor reduces the affinity of RNA polymerase for nonspecific DNA while increasing specificity for promoters, allowing transcription to initiate at correct sites. The core enzyme of RNA polymerase has five subunits (protein subunits) (~400 kDa).{{cite journal | last1 = Ebright|first1= Richard H. |authorlink1=Richard H. Ebright| title = RNA polymerase: structural similarities between bacterial RNA polymerase and eukaryotic RNA polymerase II | journal = Journal of Molecular Biology | volume = 304 | issue = 5 | pages = 687–98 | date = December 2000 | pmid = 11124018 | doi = 10.1006/jmbi.2000.4309 }} Because of the RNA polymerase association with sigma factor, the complete RNA polymerase therefore has 6 subunits: the sigma subunit-in addition to the two alpha (α), one beta (β), one beta prime (β'), and one omega (ω) subunits that make up the core enzyme(~450 kDa). In addition, many bacteria can have multiple alternative σ factors. The level and activity of the alternative σ factors are highly regulated and can vary depending on environmental or developmental signals.{{ cite book |last1= Chandrangsu|first1= Pete| last2=Helmann |first2=John D. | date = March 2014 | chapter = Sigma factors in gene expression | title = Encyclopedia of Life Sciences | publisher = John Wiley & Sons Ltd | location = Chichester | doi = 10.1002/9780470015902.a0000854.pub3 | isbn = 978-0-470-01590-2 }}

{{main|Transcription preinitiation complex}}

The transcription preinitiation complex is a large complex of proteins that is necessary for the transcription of protein-coding genes in eukaryotes and archaea. It attaches to the promoter of the DNA (e.i., TATA box) and helps position the RNA polymerase II to the gene transcription start sites, denatures the DNA, and then starts transcription.{{cite journal |last1=Kornberg |first1=Roger D. |title=The molecular basis of eukaryotic transcription |journal=Proceedings of the National Academy of Sciences of the United States of America |date=7 August 2007 |volume=104 |issue=32 |pages=12955–61 |doi=10.1073/pnas.0704138104 |pmid=17670940 |pmc=1941834|bibcode=2007PNAS..10412955K |doi-access=free }}{{cite journal |last1=Kim |first1=Tae-Kyung |last2=Lagrange |first2=Thierry |last3=Wang |first3=Yuh-Hwa |last4=Griffith |first4=Jack D. |last5=Reinberg |first5=Danny |last6=Ebright |first6=Richard H. |authorlink6=Richard H. Ebright |title=Trajectory of DNA in the RNA polymerase II transcription preinitiation complex |journal=Proceedings of the National Academy of Sciences of the United States of America |date=11 November 1997 |volume=94 |issue=23 |pages=12268–73 |doi=10.1073/pnas.94.23.12268 |pmid=9356438 |pmc=24903|bibcode=1997PNAS...9412268K |doi-access=free }}{{cite journal | last1=Kim |first1=Tae-Kyung |last2=Ebright|first2= Richard H.|last3= Reinberg |first3=Danny | title = Mechanism of ATP-dependent promoter melting by transcription factor IIH | journal = Science | volume = 288 | issue = 5470 | pages = 1418–22 | date = May 2000 | pmid = 10827951 | doi = 10.1126/science.288.5470.1418 | authorlink2 = Richard H. Ebright |bibcode=2000Sci...288.1418K }}

The assembly of transcription preinitiation complex follows these steps:

1. TATA binding protein (TBP), a subunit of TFIID (the largest GTF) binds to the promoter (TATA box), creating a sharp bend in the promoter DNA. Then the TBP-TFIIA interactions recruit TFIIA to the promoter.
2. TBP-TFIIB interactions recruit TFIIB to the promoter. RNA polymerase II and TFIIF assemble to form the Polymerase II complex. TFIIB helps the Pol II complex bind correctly.
3. TFIIE and TFIIH then bind to the complex and form the transcription preinitiation complex. TFIIA/B/E/H leave once RNA elongation begins. TFIID will stay until elongation is finished.
4. Subunits within TFIIH that have ATPase and helicase activity create negative superhelical tension in the DNA. This negative superhelical tension causes approximately one turn of DNA to unwind and form the transcription bubble.
5. The template strand of the transcription bubble engages with the RNA polymerase II active site, then RNA synthesis starts.

{{Reflist}}

• {{MeshName|General+Transcription+Factors}}
• [https://www.nlm.nih.gov/cgi/mesh/2011/MB_cgi?mode=&index=18578&field=all&HM=&II=&PA=&form=&input= Holoenzymes] at the US National Library of Medicine Medical Subject Headings
• [https://www.youtube.com/watch?v=SMtWvDbfHLo DNA Transcription YouTube Video]

{{Cell signaling}}

{{Transcription factors|g2}}

{{DEFAULTSORT:General Transcription Factor}}

Category:Transcription factors