General transcription factors (GTFs), also known as basal transcriptional factors, are a class of proteintranscription factors that bind to specific sites (promoter) on DNA to activate transcription of genetic information from DNA to messenger RNA. GTFs, RNA polymerase, and the mediator (a multi-protein complex) constitute the basic transcriptional apparatus that first bind to the promoter, then start transcription.[1] GTFs are also intimately involved in the process of gene regulation, and most are required for life.[2]
Transcription factors. In the middle part above the promoter, the pink color part of the transcription factors are the General Transcription Factors.
A transcription factor is a protein that binds to specific DNA sequences (enhancer or promoter), either alone or with other proteins in a complex, to control the rate of transcription of genetic information from DNA to messenger RNA by promoting (serving as an activator) or blocking (serving as a repressor) the recruitment of RNA polymerase.[3][4][5][6][7] As a class of protein, general transcription factors bind to promoters along the DNA sequence or form a large transcription preinitiation complex to activate transcription. General transcription factors are necessary for transcription to occur.[8][9][10]
In bacteria, transcription initiation requires an RNA polymerase and a single GTF: sigma factor.
Transcription preinitiation complex
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:[7][11]
TFIIA – stabilizes the interaction between the TATA box and TFIID/TATA binding protein (TBP)
A sigma factor is a protein needed only for initiation of RNA synthesis in bacteria.[12] 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.[13] 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).[14] 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.[15]
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.[7][16][17][18]
Transcription preinitiation complex assemblyedit
The assembly of transcription preinitiation complex follows these steps:
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.
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.
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.
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.
The template strand of the transcription bubble engages with the RNA polymerase II active site, then RNA synthesis starts.
Referencesedit
^Pierce, Benjamin A. (2012). Genetics a conceptual approach (4th ed.). New York: W.H. Freeman. pp. 364–367. ISBN978-1-4292-3250-0.
^Dillon, Niall (2006). "Gene regulation and large-scale chromatin organization in the nucleus". Chromosome Research. 14 (1): 117–26. doi:10.1007/s10577-006-1027-8. PMID 16506101. S2CID 28667905.
^Karin, M. (February 1990). "Too many transcription factors: positive and negative interactions". The New Biologist. 2 (2): 126–31. PMID 2128034.
^Roeder, Robert G. (September 1996). "The role of general initiation factors in transcription by RNA polymerase II". Trends in Biochemical Sciences. 21 (9): 327–35. doi:10.1016/S0968-0004(96)10050-5. PMID 8870495.
^ abcLee, Tong Ihn; Young, Richard A. (2000). "Transcription of eukaryotic protein-coding genes". Annual Review of Genetics. 34 (1): 77–137. doi:10.1146/annurev.genet.34.1.77. PMID 11092823.
^Weinzierl, Robert O.J. (1999). Mechanisms of Gene Expression: Structure, Function and Evolution of the Basal Transcriptional Machinery. London: Imperial College Press. ISBN978-1-86094-126-9.
^Shilatifard, Ali; Conaway, Ronald C.; Conaway, Joan Weliky (2003). "The RNA polymerase II elongation complex". Annual Review of Biochemistry. 72 (1): 693–715. doi:10.1146/annurev.biochem.72.121801.161551. PMID 12676794.
^Orphanides, George; Lagrange, Thierry; Reinberg, Danny (November 1996). "The general transcription factors of RNA polymerase II". Genes & Development. 10 (21): 2657–83. doi:10.1101/gad.10.21.2657. PMID 8946909.
^Gruber, Tanja M.; Gross, Carol A. (October 2003). "Multiple sigma subunits and the partitioning of bacterial transcription space". Annual Review of Microbiology. 57: 441–66. doi:10.1146/annurev.micro.57.030502.090913. PMID 14527287.
^Borukhov, Sergei; Nudler, Evgeny (April 2003). "RNA polymerase holoenzyme: structure, function and biological implications". Current Opinion in Microbiology. 6 (2): 93–100. doi:10.1016/S1369-5274(03)00036-5. ISSN 1369-5274. PMID 12732296.
^Ebright, Richard H. (December 2000). "RNA polymerase: structural similarities between bacterial RNA polymerase and eukaryotic RNA polymerase II". Journal of Molecular Biology. 304 (5): 687–98. doi:10.1006/jmbi.2000.4309. PMID 11124018.
^Chandrangsu, Pete; Helmann, John D. (March 2014). "Sigma factors in gene expression". Encyclopedia of Life Sciences. Chichester: John Wiley & Sons Ltd. doi:10.1002/9780470015902.a0000854.pub3. ISBN978-0-470-01590-2.
^Kim, Tae-Kyung; Ebright, Richard H.; Reinberg, Danny (May 2000). "Mechanism of ATP-dependent promoter melting by transcription factor IIH". Science. 288 (5470): 1418–22. Bibcode:2000Sci...288.1418K. doi:10.1126/science.288.5470.1418. PMID 10827951.
External linksedit
General+Transcription+Factors at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
Holoenzymes at the US National Library of Medicine Medical Subject Headings
DNA Transcription YouTube Video
January 01, 1970
general, transcription, factor, gtfs, also, known, basal, transcriptional, factors, class, protein, transcription, factors, that, bind, specific, sites, promoter, activate, transcription, genetic, information, from, messenger, gtfs, polymerase, mediator, multi. General transcription factors GTFs also known as basal transcriptional factors are a class of protein transcription factors that bind to specific sites promoter on DNA to activate transcription of genetic information from DNA to messenger RNA GTFs RNA polymerase and the mediator a multi protein complex constitute the basic transcriptional apparatus that first bind to the promoter then start transcription 1 GTFs are also intimately involved in the process of gene regulation and most are required for life 2 Transcription factors In the middle part above the promoter the pink color part of the transcription factors are the General Transcription Factors A transcription factor is a protein that binds to specific DNA sequences enhancer or promoter either alone or with other proteins in a complex to control the rate of transcription of genetic information from DNA to messenger RNA by promoting serving as an activator or blocking serving as a repressor the recruitment of RNA polymerase 3 4 5 6 7 As a class of protein general transcription factors bind to promoters along the DNA sequence or form a large transcription preinitiation complex to activate transcription General transcription factors are necessary for transcription to occur 8 9 10 Contents 1 Types 2 Function and mechanism 2 1 In bacteria 2 2 In archaea and eukaryotes 2 2 1 Transcription preinitiation complex assembly 3 References 4 External linksTypes editIn bacteria transcription initiation requires an RNA polymerase and a single GTF sigma factor nbsp Transcription preinitiation complex 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 7 11 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 promoterFunction and mechanism editIn bacteria edit Main article Sigma factor A sigma factoris a protein needed only for initiation of RNA synthesis in bacteria 12 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 13 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 14 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 a one beta b one beta prime b and one omega w subunits that make up the core enzyme 450 kDa In addition many bacteria can have multiple alternative s factors The level and activity of the alternative s factors are highly regulated and can vary depending on environmental or developmental signals 15 In archaea and eukaryotes edit Main article 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 7 16 17 18 Transcription preinitiation complex assembly edit The assembly of transcription preinitiation complex follows these steps 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 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 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 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 The template strand of the transcription bubble engages with the RNA polymerase II active site then RNA synthesis starts References edit Pierce Benjamin A 2012 Genetics a conceptual approach 4th ed New York W H Freeman pp 364 367 ISBN 978 1 4292 3250 0 Dillon Niall 2006 Gene regulation and large scale chromatin organization in the nucleus Chromosome Research 14 1 117 26 doi 10 1007 s10577 006 1027 8 PMID 16506101 S2CID 28667905 Latchman David S December 1997 Transcription factors an overview The International Journal of Biochemistry amp Cell Biology 29 12 1305 12 doi 10 1016 S1357 2725 97 00085 X PMC 2002184 PMID 9570129 Karin M February 1990 Too many transcription factors positive and negative interactions The New Biologist 2 2 126 31 PMID 2128034 Roeder Robert G September 1996 The role of general initiation factors in transcription by RNA polymerase II Trends in Biochemical Sciences 21 9 327 35 doi 10 1016 S0968 0004 96 10050 5 PMID 8870495 Nikolov D B Burley S K 1997 RNA polymerase II transcription initiation A structural view Proceedings of the National Academy of Sciences of the United States of America 94 1 15 22 Bibcode 1997PNAS 94 15N doi 10 1073 pnas 94 1 15 PMC 33652 PMID 8990153 a b c Lee Tong Ihn Young Richard A 2000 Transcription of eukaryotic protein coding genes Annual Review of Genetics 34 1 77 137 doi 10 1146 annurev genet 34 1 77 PMID 11092823 Weinzierl Robert O J 1999 Mechanisms of Gene Expression Structure Function and Evolution of the Basal Transcriptional Machinery London Imperial College Press ISBN 978 1 86094 126 9 Reese Joseph C April 2003 Basal transcription factors Current Opinion in Genetics amp Development 13 2 114 8 doi 10 1016 S0959 437X 03 00013 3 PMID 12672487 Shilatifard Ali Conaway Ronald C Conaway Joan Weliky 2003 The RNA polymerase II elongation complex Annual Review of Biochemistry 72 1 693 715 doi 10 1146 annurev biochem 72 121801 161551 PMID 12676794 Orphanides George Lagrange Thierry Reinberg Danny November 1996 The general transcription factors of RNA polymerase II Genes amp Development 10 21 2657 83 doi 10 1101 gad 10 21 2657 PMID 8946909 nbsp Gruber Tanja M Gross Carol A October 2003 Multiple sigma subunits and the partitioning of bacterial transcription space Annual Review of Microbiology 57 441 66 doi 10 1146 annurev micro 57 030502 090913 PMID 14527287 Borukhov Sergei Nudler Evgeny April 2003 RNA polymerase holoenzyme structure function and biological implications Current Opinion in Microbiology 6 2 93 100 doi 10 1016 S1369 5274 03 00036 5 ISSN 1369 5274 PMID 12732296 Ebright Richard H December 2000 RNA polymerase structural similarities between bacterial RNA polymerase and eukaryotic RNA polymerase II Journal of Molecular Biology 304 5 687 98 doi 10 1006 jmbi 2000 4309 PMID 11124018 Chandrangsu Pete Helmann John D March 2014 Sigma factors in gene expression Encyclopedia of Life Sciences Chichester John Wiley amp Sons Ltd doi 10 1002 9780470015902 a0000854 pub3 ISBN 978 0 470 01590 2 Kornberg Roger D 7 August 2007 The molecular basis of eukaryotic transcription Proceedings of the National Academy of Sciences of the United States of America 104 32 12955 61 Bibcode 2007PNAS 10412955K doi 10 1073 pnas 0704138104 PMC 1941834 PMID 17670940 Kim Tae Kyung Lagrange Thierry Wang Yuh Hwa Griffith Jack D Reinberg Danny Ebright Richard H 11 November 1997 Trajectory of DNA in the RNA polymerase II transcription preinitiation complex Proceedings of the National Academy of Sciences of the United States of America 94 23 12268 73 Bibcode 1997PNAS 9412268K doi 10 1073 pnas 94 23 12268 PMC 24903 PMID 9356438 Kim Tae Kyung Ebright Richard H Reinberg Danny May 2000 Mechanism of ATP dependent promoter melting by transcription factor IIH Science 288 5470 1418 22 Bibcode 2000Sci 288 1418K doi 10 1126 science 288 5470 1418 PMID 10827951 External links editGeneral Transcription Factors at the U S National Library of Medicine Medical Subject Headings MeSH Holoenzymes at the US National Library of Medicine Medical Subject Headings DNA Transcription YouTube Video Retrieved from https en wikipedia org w index php title General transcription factor amp oldid 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