General transcription factor

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Transcription factors. In the middle part above the promoter, the pink color part of the transcription factors are the General Transcription Factors. Transcription Factors.svg
Transcription factors. In the middle part above the promoter, the pink color part of the transcription factors are the General Transcription Factors.

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]

Contents

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]

Types

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

Transcription preinitiation complex Preinitiation complex.png
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]

Function and mechanism

In bacteria

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]

In archaea and eukaryotes

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

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.

Related Research Articles

In molecular biology, the TATA box is a sequence of DNA found in the core promoter region of genes in archaea and eukaryotes. The bacterial homolog of the TATA box is called the Pribnow box which has a shorter consensus sequence.

<span class="mw-page-title-main">Transcription preinitiation complex</span> Complex of proteins necessary for gene transcription in eukaryotes and archaea

The preinitiation complex is a complex of approximately 100 proteins that is necessary for the transcription of protein-coding genes in eukaryotes and archaea. The preinitiation complex positions RNA polymerase II at gene transcription start sites, denatures the DNA, and positions the DNA in the RNA polymerase II active site for transcription.

<span class="mw-page-title-main">TATA-binding protein</span> Protein-coding gene in the species Homo sapiens

The TATA-binding protein (TBP) is a general transcription factor that binds specifically to a DNA sequence called the TATA box. This DNA sequence is found about 30 base pairs upstream of the transcription start site in some eukaryotic gene promoters.

Transcription factor II D (TFIID) is one of several general transcription factors that make up the RNA polymerase II preinitiation complex. RNA polymerase II holoenzyme is a form of eukaryotic RNA polymerase II that is recruited to the promoters of protein-coding genes in living cells. It consists of RNA polymerase II, a subset of general transcription factors, and regulatory proteins known as SRB proteins. Before the start of transcription, the transcription Factor II D (TFIID) complex binds to the core promoter DNA of the gene through specific recognition of promoter sequence motifs, including the TATA box, Initiator, Downstream Promoter, Motif Ten, or Downstream Regulatory elements.

<span class="mw-page-title-main">Eukaryotic transcription</span> Transcription is heterocatalytic function of DNA

Eukaryotic transcription is the elaborate process that eukaryotic cells use to copy genetic information stored in DNA into units of transportable complementary RNA replica. Gene transcription occurs in both eukaryotic and prokaryotic cells. Unlike prokaryotic RNA polymerase that initiates the transcription of all different types of RNA, RNA polymerase in eukaryotes comes in three variations, each translating a different type of gene. A eukaryotic cell has a nucleus that separates the processes of transcription and translation. Eukaryotic transcription occurs within the nucleus where DNA is packaged into nucleosomes and higher order chromatin structures. The complexity of the eukaryotic genome necessitates a great variety and complexity of gene expression control.

Transcription factor TFIIA is a nuclear protein involved in the RNA polymerase II-dependent transcription of DNA. TFIIA is one of several general (basal) transcription factors (GTFs) that are required for all transcription events that use RNA polymerase II. Other GTFs include TFIID, a complex composed of the TATA binding protein TBP and TBP-associated factors (TAFs), as well as the factors TFIIB, TFIIE, TFIIF, and TFIIH. Together, these factors are responsible for promoter recognition and the formation of a transcription preinitiation complex (PIC) capable of initiating RNA synthesis from a DNA template.

<span class="mw-page-title-main">Transcription factor II B</span> Mammalian protein found in Homo sapiens

Transcription factor II B (TFIIB) is a general transcription factor that is involved in the formation of the RNA polymerase II preinitiation complex (PIC) and aids in stimulating transcription initiation. TFIIB is localised to the nucleus and provides a platform for PIC formation by binding and stabilising the DNA-TBP complex and by recruiting RNA polymerase II and other transcription factors. It is encoded by the TFIIB gene, and is homologous to archaeal transcription factor B and analogous to bacterial sigma factors.

Transcription factor II E (TFIIE) is one of several general transcription factors that make up the RNA polymerase II preinitiation complex. It is a tetramer of two alpha and two beta chains and interacts with TAF6/TAFII80, ATF7IP, and varicella-zoster virus IE63 protein.

Transcription factor II F (TFIIF) is one of several general transcription factors that make up the RNA polymerase II preinitiation complex.

<span class="mw-page-title-main">TAF6</span> Protein-coding gene in the species Homo sapiens

Transcription initiation factor TFIID subunit 6 is a protein that in humans is encoded by the TAF6 gene.

<span class="mw-page-title-main">TAF7</span> Protein-coding gene in the species Homo sapiens

Transcription initiation factor TFIID subunit 7 also known as TAFII55 is a protein that in humans is encoded by the TAF7 gene.

<span class="mw-page-title-main">TAF4</span> Protein-coding gene in the species Homo sapiens

Transcription initiation factor TFIID subunit 4 is a protein that in humans is encoded by the TAF4 gene.

<span class="mw-page-title-main">TAF2</span> Protein-coding gene in the species Homo sapiens

Transcription initiation factor TFIID subunit 2 is a protein that in humans is encoded by the TAF2 gene.

<span class="mw-page-title-main">TAF10</span> Protein-coding gene in the species Homo sapiens

Transcription initiation factor TFIID subunit 10 is a protein that in humans is encoded by the TAF10 gene.

<span class="mw-page-title-main">TAF5</span> Protein-coding gene in the species Homo sapiens

Transcription initiation factor TFIID subunit 5 is a protein that in humans is encoded by the TAF5 gene.

<span class="mw-page-title-main">TAF11</span> Protein-coding gene in the species Homo sapiens

Transcription initiation factor TFIID subunit 11 also known as TAFII28, is a protein that in humans is encoded by the TAF11 gene.

<span class="mw-page-title-main">TAF15</span> Protein-coding gene in the species Homo sapiens

TATA-binding protein-associated factor 2N is a protein that in humans is encoded by the TAF15 gene.

<span class="mw-page-title-main">TAF13</span> Protein-coding gene in the species Homo sapiens

Transcription initiation factor TFIID subunit 13 is a protein that in humans is encoded by the TAF13 gene.

RNA polymerase II holoenzyme is a form of eukaryotic RNA polymerase II that is recruited to the promoters of protein-coding genes in living cells. It consists of RNA polymerase II, a subset of general transcription factors, and regulatory proteins known as SRB proteins.

<span class="mw-page-title-main">Archaeal transcription factor B</span> Protein family

Archaeal transcription factor B is a protein family of extrinsic transcription factors that guide the initiation of RNA transcription in organisms that fall under the domain of Archaea. It is homologous to eukaryotic TFIIB and, more distantly, to bacterial sigma factor. Like these proteins, it is involved in forming transcription preinitiation complexes. Its structure includes several conserved motifs which interact with DNA and other transcription factors, notably the single type of RNA polymerase that performs transcription in Archaea.

References

  1. ↑ Pierce, Benjamin A. (2012). Genetics a conceptual approach (4th ed.). New York: W.H. Freeman. pp.  364–367. ISBN   978-1-4292-3250-0.
  2. ↑ 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.
  3. ↑ Latchman, David S. (December 1997). "Transcription factors: an overview". The International Journal of Biochemistry & Cell Biology . 29 (12): 1305–12. doi:10.1016/S1357-2725(97)00085-X. PMC   2002184 . PMID   9570129.
  4. ↑ Karin, M. (February 1990). "Too many transcription factors: positive and negative interactions". The New Biologist. 2 (2): 126–31. PMID   2128034.
  5. ↑ 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.
  6. ↑ 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.
  7. 1 2 3 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.
  8. ↑ 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.
  9. ↑ Reese, Joseph C. (April 2003). "Basal transcription factors". Current Opinion in Genetics & Development . 13 (2): 114–8. doi:10.1016/S0959-437X(03)00013-3. PMID   12672487.
  10. ↑ 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.
  11. ↑ 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. Open Access logo PLoS transparent.svg
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 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. ISBN   978-0-470-01590-2.
  16. ↑ 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.
  17. ↑ 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.
  18. ↑ 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.
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