Gene transcription factors

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Editor-In-Chief: Henry A. Hoff

A transcription factor is a protein that binds to specific DNA sequences to control the flow (or transcription) of genetic information from DNA to messenger RNA (mRNA).[1][2]

Transcription factors perform this function alone or with other proteins in a complex, by promoting (as an activator), or blocking (as a repressor) the recruitment of RNA polymerase (the enzyme that performs the transcription of genetic information from DNA to RNA) to specific genes.[3][4][5]

Genetics

Main article: Genetics
File:Bob, the guinea pig.jpg
This is an image of Bob, the guinea pig. Credit: selbst.
File:Peruvian cavy.jpg
This guinea pig has gorgeous long hair and was a prize winner at the Puyallup, WA fair. Credit: Christine from Washington State, USA.

Genetics involves the expression, transmission, and variation of inherited characteristics.

Def. a "branch of biology that deals with the transmission and variation of inherited characteristics, in particular chromosomes and DNA"[6] is called genetics.

Gene transcriptions

Main article: Gene transcriptions

Once the DNA double helix and its associated epigenome have been melted so that the template strand is available for binding, a transcription factor binds to a specific nucleotide sequence to biochemically influence gene transcription.

Transcription factor glossary
• coactivator – a protein that works with transcription factors to increase the rate of gene transcription
• corepressor – a protein that works with transcription factors to decrease the rate of gene transcription
• downregulation, repression, or suppression – decrease the rate of gene transcription
• factor – a substance, such as a protein, that contributes to the cause of a specific biochemical reaction or bodily process
• general transcription factor – a transcription factor that activates gene transcription
• gene transcription - copying of DNA into messenger RNA by RNA polymerase
• transcriptional regulation – modulating the rate of gene transcription
• upregulation, activation, or promotion – increase the rate of gene transcription
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Theoretical transcription factors

Def. a substance that contains one or more DNA-binding domains that are nucleotide-sequence specific is called a transcription factor.

Def. a protein that binds to specific DNA sequences, thereby controlling the flow (or transcription) of genetic information from DNA to mRNA is called a transcription factor.

DNA-binding domains

There are approximately 2600 proteins in the human genome that contain DNA-binding domains, and most of these are presumed to function as transcription factors,[7] though other studies indicate it to be a smaller number.[8] Therefore, approximately 10% of genes in the genome code for transcription factors, which makes this family the single largest family of human proteins. Furthermore, genes are often flanked by several binding sites for distinct transcription factors, and efficient expression of each of these genes requires the cooperative action of several different transcription factors (see, for example, hepatocyte nuclear factors). Hence, the combinatorial use of a subset of the approximately 2000 human transcription factors easily accounts for the unique regulation of each gene in the human genome during development.[9]

A DNA-binding domain (DBD) is an independently folded protein domain that contains at least one motif that recognizes double- or single-stranded DNA. A DBD can recognize a specific DNA sequence (a recognition sequence) or have a general affinity to DNA.[10]

Examples of specific transcription factor DBDs[11]
Factor Structural type Recognition sequence Consensus sequence Binds as
Sp1 transcription factor (SP1) Zinc finger 5'-GGGCGG-3' 5'-(G/T)GGGCGG(G/A)(G/A)(C/T)-3' Monomer
AP-1 transcription factor (AP-1) Basic zipper 5'-TGA(G/C)TCA-3' 5'-TGA G/C TCA-3'.[12] Dimer
Ccaat-enhancer-binding proteins (C/EBP) Basic zipper 5'-ATTGCGCAAT-3' CCAAT box Dimer
Heat shock factor Basic zipper 5'-XGAAX-3' three oppositely oriented "AGAAN" motifs or a degenerate version thereof Trimer
ATF/CREB Basic zipper 5'-TGACGTCA-3' CRE box Dimer
c-Myc Basic helix-loop-helix 5'-CACGTG-3' E-box (Enhancer Box) Dimer
POU2F1 (Oct-1) Helix-turn-helix 5'-ATGCAAAT-3' 5'-ATGCAAAT-3' Monomer
Nuclear factor 1 (NF-1) Novel 5'-TTGGCXXXXXGCCAA-3' 5'-TTGGCXXXXXGCCAA-3' Dimer
(G/C) = G or C
X = A, T, G or C

Regulatory functions

Transcription factors have been classified according to their regulatory function:[13]

  • I. constitutively active – present in all cells at all times – general transcription factors, Sp1 transcription factor (Sp1), Nuclear factor 1 (NF1), Ccaat-enhancer-binding proteins (CCAAT)
  • II. conditionally active – requires activation
    • II.A developmental (cell specific) – expression is tightly controlled, but, once expressed, require no additional activation – GATA transcription factor (GATA), hepatocyte nuclear factors (HNF), PIT-1, MyoD, Myf5, Hox, winged-helix transcription factors
    • II.B signal-dependent – requires external signal for activation
      • II.B.1 extracellular ligand (endocrine or paracrine)-dependent – nuclear receptors
      • II.B.2 intracellular ligand (autocrine)-dependent - activated by small intracellular molecules – Sterol regulatory element binding protein (SREBP), p53, orphan nuclear receptors
      • II.B.3 cell membrane receptor-dependent – second messenger signaling cascades resulting in the phosphorylation of the transcription factor
        • II.B.3.a resident nuclear factors – reside in the nucleus regardless of activation state – CREB, AP-1, Mef2
        • II.B.3.b latent cytoplasmic factors – inactive form reside in the cytoplasm, but, when activated, are translocated into the nucleus – STAT, R-SMAD, NF-κB, Notch, TUBBY, NFAT

Sequence similarity

Transcription factors are often classified based on the sequence similarity and hence the tertiary structure of their DNA-binding domains:[14][15][16][17]

  • 1 Superclass: Basic Domains
    • 1.1 Class: Leucine zipper factors (bZIP)
      • 1.1.1 Family: AP-1(-like) components; includes (c-Fos/c-Jun)
      • 1.1.2 Family: CREB
      • 1.1.3 Family: Ccaat-enhancer-binding proteins (C/EBP)-like factors
      • 1.1.4 Family: bZIP / PAR
      • 1.1.5 Family: Plant G-box binding factors
      • 1.1.6 Family: ZIP only
    • 1.2 Class: Helix-loop-helix factors (bHLH)
      • 1.2.1 Family: Ubiquitous (class A) factors
      • 1.2.2 Family: Myogenic transcription factors (MyoD)
      • 1.2.3 Family: Achaete-Scute
      • 1.2.4 Family: Tal/Twist/Atonal/Hen
    • 1.3 Class: Helix-loop-helix / leucine zipper factors (basic helix-loop-helix leucine zipper transcription factors (bHLH-ZIP))
      • 1.3.1 Family: Ubiquitous bHLH-ZIP factors; includes USF (USF1, USF2); SREBP (Sterol regulatory element binding protein (SREBP))
      • 1.3.2 Family: Cell-cycle controlling factors; includes Myc (c-Myc)
    • 1.4 Class: NF-1
      • 1.4.1 Family: NF-1 (NFIA, NFIB, NFIC, NFIX)
    • 1.5 Class: RF-X
      • 1.5.1 Family: RF-X (RFX1, RFX2, RFX3, RFX4, RFX5, RFXANK)
    • 1.6 Class: bHSH
  • 2 Superclass: Zinc-coordinating DNA-binding domains
    • 2.1 Class: Cys4 zinc finger of nuclear receptor type
      • 2.1.1 Family: Steroid hormone receptors
      • 2.1.2 Family: Thyroid hormone receptor-like factors
    • 2.2 Class: diverse Cys4 zinc fingers
      • 2.2.1 Family: GATA-Factors
    • 2.3 Class: Cys2His2 zinc finger domain
      • 2.3.1 Family: Ubiquitous factors, includes TFIIIA, Sp1
      • 2.3.2 Family: Developmental / cell cycle regulators; includes Krüppel
      • 2.3.4 Family: Large factors with NF-6B-like binding properties
    • 2.4 Class: Cys6 cysteine-zinc cluster
    • 2.5 Class: Zinc fingers of alternating composition
  • 3 Superclass: Helix-turn-helix
    • 3.1 Class: Homeobox (Homeo domain)
      • 3.1.1 Family: Homeo domain only; includes Ubx
      • 3.1.2 Family: POU family (POU domain) factors; includes Octamer transcription factor (Oct)
      • 3.1.3 Family: Homeo domain with LIM region
      • 3.1.4 Family: homeo domain plus zinc finger motifs
    • 3.2 Class: Paired box
      • 3.2.1 Family: Paired plus homeo domain
      • 3.2.2 Family: Paired domain only
    • 3.3 Class: FOX proteins (Fork head) / winged helix
      • 3.3.1 Family: Developmental regulators; includes forkhead
      • 3.3.2 Family: Tissue-specific regulators
      • 3.3.3 Family: Cell-cycle controlling factors
      • 3.3.0 Family: Other regulators
    • 3.4 Class: Heat Shock Factors
      • 3.4.1 Family: HSF
    • 3.5 Class: Tryptophan clusters
      • 3.5.1 Family: Myb
      • 3.5.2 Family: Ets-type
      • 3.5.3 Family: Interferon regulatory factors
    • 3.6 Class: TEA (transcriptional enhancer factor) domain
      • 3.6.1 Family: TEA (TEAD1, TEAD2, TEAD3, TEAD4)
  • 4 Superclass: beta-Scaffold Factors with Minor Groove Contacts
    • 4.1 Class: RHR (Rel homology region)
      • 4.1.1 Family: Rel/ankyrin; NF-κB
      • 4.1.2 Family: ankyrin only
      • 4.1.3 Family: NFAT (Nuclear Factor of Activated T-cells) (NFATC1, NFATC2, NFATC3, NFATC4, NFAT5)
    • 4.2 Class: STAT
      • 4.2.1 Family: STAT
    • 4.3 Class: p53
      • 4.3.1 Family: p53
    • 4.4 Class: MADS box
      • 4.4.1 Family: Regulators of differentiation; includes (Mef2)
      • 4.4.2 Family: Responders to external signals, SRF (serum response factor)
      • 4.4.3 Family: Metabolic regulators (ARG80)
    • 4.5 Class: beta-Barrel alpha-helix transcription factors
    • 4.6 Class: TATA binding proteins
      • 4.6.1 Family: TBP
    • 4.7 Class: HMG-box
      • 4.7.1 Family: SOX genes, SRY
      • 4.7.2 Family: TCF-1 (HNF1A specifically TCF1)
      • 4.7.3 Family: HMG2-related, Structure specific recognition protein 1 (SSRP1)
      • 4.7.4 Family: UBF
      • 4.7.5 Family: MATA
    • 4.8 Class: Heteromeric CCAAT factors
      • 4.8.1 Family: Heteromeric CCAAT factors
    • 4.9 Class: Grainyhead
      • 4.9.1 Family: Grainyhead
    • 4.10 Class: Cold-shock domain factors
      • 4.10.1 Family: csd
    • 4.11 Class: Runt
      • 4.11.1 Family: Runt
  • 0 Superclass: Other Transcription Factors
    • 0.1 Class: Copper fist proteins
    • 0.2 Class: HMGI(Y) (HMGA1)
      • 0.2.1 Family: HMGI(Y)
    • 0.3 Class: Pocket domain
    • 0.4 Class: E1A-like factors
    • 0.5 Class: AP2/EREBP-related factors
      • 0.5.1 Family: Apetala 2 (AP2)
      • 0.5.2 Family: EREBP
      • 0.5.3 Superfamily: B3 DNA-binding domain (AP2/B3)
        • 0.5.3.1 Family: ARF
        • 0.5.3.2 Family: ABI
        • 0.5.3.3 Family: RAV

General transcription factors

Main articles: Gene transcriptions/General factors and 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 on DNA to activate transcription. GTFs, RNA polymerase, and the mediator multiple protein complex constitute the basic transcriptional apparatus.[18]"[19]

Hypotheses

Main article: Hypotheses
  1. Some transcription factors transcribe A1BG.

See also

References

  1. ↑ Latchman DS (1997). "Transcription factors: an overview". Int. J. Biochem. Cell Biol. 29 (12): 1305–12. doi:10.1016/S1357-2725(97)00085-X. PMID 9570129.
  2. ↑ Karin M (1990). "Too many transcription factors: positive and negative interactions". New Biol. 2 (2): 126–31. PMID 2128034.
  3. ↑ Roeder RG (1996). "The role of general initiation factors in transcription by RNA polymerase II". Trends Biochem. Sci. 21 (9): 327–35. doi:10.1016/0968-0004(96)10050-5. PMID 8870495.
  4. ↑ Nikolov DB, Burley SK (1997). "RNA polymerase II transcription initiation: A structural view". Proc. Natl. Acad. Sci. U.S.A. 94 (1): 15–22. doi:10.1073/pnas.94.1.15. PMC 33652. PMID 8990153.
  5. ↑ Lee TI, Young RA (2000). "Transcription of eukaryotic protein-coding genes". Annu. Rev. Genet. 34: 77–137. doi:10.1146/annurev.genet.34.1.77. PMID 11092823.
  6. ↑ genetics. San Francisco, California: Wikimedia Foundation, Inc. April 16, 2014. Retrieved 2014-05-07.
  7. ↑ Babu MM, Luscombe NM, Aravind L, Gerstein M, Teichmann SA (2004). "Structure and evolution of transcriptional regulatory networks". Curr. Opin. Struct. Biol. 14 (3): 283–91. doi:10.1016/j.sbi.2004.05.004. PMID 15193307.
  8. ↑ http://www.biostars.org/p/53590/
  9. ↑ Brivanlou AH, Darnell JE (2002). "Signal transduction and the control of gene expression". Science. 295 (5556): 813–8. doi:10.1126/science.1066355. PMID 11823631.
  10. ↑ Lilley, David M. J. (1995). DNA-protein: structural interactions. Oxford: IRL Press at Oxford University Press. ISBN 0-19-963453-X.
  11. ↑ Walter F. Boron (2003). Medical Physiology: A Cellular And Molecular Approach. Elsevier/Saunders. pp. 125–126. ISBN 1-4160-2328-3.
  12. ↑ Angel, P; Imagawa, M; Chiu, R; Stein, B; Imbra, RJ; Rahmsdorf, HJ; Jonat, C; Herrlich, P; Karin, M (19 June 1987). "Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor". Cell. 49 (6): 729–39. doi:10.1016/0092-8674(87)90611-8. PMID 3034432.
  13. ↑ Brivanlou AH, Darnell JE (February 2002). "Signal transduction and the control of gene expression". Science. 295 (5556): 813–8. Bibcode:2002Sci...295..813B. doi:10.1126/science.1066355. PMID 11823631.
  14. ↑ Stegmaier P, Kel AE, Wingender E (2004). "Systematic DNA-binding domain classification of transcription factors". Genome Informatics. International Conference on Genome Informatics. 15 (2): 276–86. PMID 15706513. Archived from the original on 19 June 2013.
  15. ↑ Matys V, Kel-Margoulis OV, Fricke E, Liebich I, Land S, Barre-Dirrie A, Reuter I, Chekmenev D, Krull M, Hornischer K, Voss N, Stegmaier P, Lewicki-Potapov B, Saxel H, Kel AE, Wingender E (January 2006). "TRANSFAC and its module TRANSCompel: transcriptional gene regulation in eukaryotes". Nucleic Acids Research. 34 (Database issue): D108–10. doi:10.1093/nar/gkj143. PMC 1347505. PMID 16381825.
  16. ↑ "TRANSFAC database". Retrieved 5 August 2007.
  17. ↑ Jin J, Zhang H, Kong L, Gao G, Luo J (January 2014). "PlantTFDB 3.0: a portal for the functional and evolutionary study of plant transcription factors". Nucleic Acids Research. 42 (Database issue): D1182–7. doi:10.1093/nar/gkt1016. PMC 3965000. PMID 24174544.
  18. ↑ Pierce, Benjamin A. 2002. Genetics : A Conceptual Approach. 1st ed. New York: W.H. Freeman and Co. pg. 367-369.
  19. ↑ "General transcription factor, In: Wikipedia". San Francisco, California: Wikimedia Foundation, Inc. August 8, 2012. Retrieved 2012-09-30.

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