Transcription Factors

Abstract

Transcription factors are regulatory proteins that can increase or decrease the transcription of a particular gene from deoxyribonucleic acid into the corresponding ribonucleic acid. They play a key role in embryonic development, the creation and maintenance of cell type‐ and tissue‐specific patterns of protein synthesis and the response to cellular signalling pathways. Transcription factors are involved in a large number of human diseases such as congenital malformations, hereditary syndromes and a myriad of benignant and malignant neoplasms. Some transcription factors in addition to their regulation of homeostatic genes control the expression of many inflammatory genes and may, therefore, play a key role in the pathogenesis of a rapidly growing number of inflammatory/autoimmune diseases contributing to determine disease severity and response to treatment.

Key Concepts

  • Transcriptional factors are proteins that regulate and activate the transcriptional response in a DNA‐dependent manner.
  • Transcription factors are classified into several families share structural characteristics.
  • Transcriptional factors play a key role in health and disease.
  • Transcription factors are involved in a large number of human diseases such as cancers.
  • The activation/repression of different transcription factors and the genetic regulation of their expression is a critical mechanism regulating the expression of different human diseases and their responsiveness to therapy.

Keywords: transcription factors; DNA binding; transcriptional activation; transcriptional repression; cellular signalling; human disease

Figure 1. Under normal conditions, HSF1 exists primarily as a latent monomer in the cytosol. Upon exposure to cytotoxic conditions such as heat shock or oxidative stress, HSF1 trimerizes and migrates to the nucleus. In the trimeric state, HSF1 binds to the HSE, forming a complex that has the potential to activate the transcription of hsp genes.
Figure 2. Structure of (a) the yeast GCN4 factor and (b) the mammalian glucocorticoid receptor, indicating the distinct regions that mediate DNA binding or transcription activation. Reproduced with permission from Adcock and Caramori . © John Wiley and Sons.
Figure 3. Histone acetylation by pro‐inflammatory transcription factors. In response to stress and other stimuli, such as cytokines, various secondary messenger systems are upregulated, leading to activation of signal‐dependent transcription factors (TF) including cAMP response element binding factor (CREB), nuclear factor‐κB, activator protein‐1 and signal transduction‐activated transcription factor (STAT) proteins. Binding of these factors leads to recruitment of CREB‐binding protein (CBP) and/or other coactivators to signal‐dependent promoters and acetylation of histones by an intrinsic acetylase activity (HAT). Induction of histone acetylation allows the formation of a more loosely packed nucleosome structure that enables access to TATA‐box binding protein (TBP) and associated factors (TAF) and the recruitment of further remodelling factors including switch/sucrose no fermentable (SWI/SNF). Remodelling thereby allows RNA polymerase II recruitment and the activation of inflammatory gene transcription. PCAF, p300/CBP associated factor. Reproduced with permission from Latchman . © John Wiley and Sons.
Figure 4. Potential mechanisms by which a transcription factor can repress gene expression. This can occur: (a) by the repressor (R) producing a tightly packed chromatin structure which prevents an activator (A) from binding; (b) by the repressor binding to the DNA‐binding site of the activator and preventing it from binding and activating gene expression; (c) by the repressor interacting with the activator in solution and preventing its DNA binding; (d) by the repressor binding to DNA with the activator and neutralising its ability to activate gene expression or (e) by direct repression by an inhibitory transcription factor. ABS: activator‐binding site. Reproduced with permission from Latchman . © John Wiley and Sons.
Figure 5. Gene activation mediated by (a) the synthesis of a transcription factor only in a specific tissue or (b) activation of the transcription factor only in a specific tissue. Reproduced with permission from Latchman . © John Wiley and Sons.
Figure 6. Mechanisms by which transcription factors can be activated by posttranslational changes. The circle represents an active transcription factor, while the square represents a no active factor. The open box represents either an inhibitory protein or a portion of the factor, which has been cleaved off in the process of activation. L: ligand; P: phosphorylation. Reproduced with permission from Latchman . © John Wiley and Sons.
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Further Reading

Latchman DS (ed.) (1997) Landmarks in Gene Regulation. Colchester, UK: Portland Press Limited.

Latchman DS (ed.) (2005) Gene Regulation: A Eukaryotic Perspective, 5th edn. NewYork: Taylor and Francis, UK.

Latchman DS (2004) Eukaryotic Transcription Factors, 4th edn, p. 360. London, UK: Elsevier/Academic Press.

Latchman DS (ed.) (1998) Transcription Factors: A Practical Approach, 2nd edn. Oxford, UK: IRL Press.

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Caramori, Gaetano, Ruggeri, Paolo, Mumby, Sharon, Atzeni, Fabiola, and Adcock, Ian M(Feb 2019) Transcription Factors. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005278.pub3]