Transcription Factors


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.


Adcock I and Caramori G (2001) Cross‐talk between pro‐inflammatory transcription factors and glucocorticoids. Immunology and Cell Biology 79: 376–384.

Adcock IM , Ito K and Barnes PJ (2004) Glucocorticoids: effects on gene transcription. Proceedings of the American Thoracic Society 1: 247–254.

Alfonso‐Gonzalez C and Riesgo‐Escovar JR (2018) Fos metamorphoses: lessons from mutants in model organisms. Mechanisms of Development 18: 30068–30069.

Asfour HA , Allouh MZ and Said RS (2018) Myogenic regulatory factors: the orchestrators of myogenesis after 30 years of discovery. Experimental Biolology and Medicine (Maywood) 243: 118–128.

Barnes PJ (2006) Transcription factors in airway diseases. Lab Invest. 86 (9): 867–872. Epub 2006 Jul 24. Review. PubMed PMID: 16865089.

Barnes PJ (2017a) Cellular and molecular mechanisms of asthma and COPD. Clinical Science 131: 1541–1558.

Barnes PJ (2017b) Glucocorticosteroids. Handbook of Experimental Pharmacology 237: 93–115.

Batie M , Del Peso L and Rocha S (2018) Hypoxia and chromatin: a focus on transcriptional repression mechanisms. Biomedicines 6: E47.

Boudjadi S , Chatterjee B , Sun W , et al. (2018) The expression and function of PAX3 in development and disease. Gene 666: 145–157.

Bouhel MA , Lambert M and David‐Cordonnier MH (2015) Targeting transcription factor binding to DNA by competing with DNA binders as an approach for controlling gene expression. Current Topics in Medicinal Chemistry 15: 1323–1358.

Caramori G , Adcock IM and Ito K (2004) Anti‐inflammatory inhibitors of IkappaB kinase in asthma and COPD. Current Opinion in Investigational Drugs 5: 1141–1147.

Caramori G , Casolari P and Adcock I (2013) Role of transcription factors in the pathogenesis of asthma and COPD. Cell Communication & Adhesion 20: 21–40.

Clayton AL , Hazzalin CA and Mahadevan LC (2006) Enhanced histone acetylation and transcription: a dynamic perspective. Molecular Cell 23: 289–296.

Courey AJ and Jia S (2001) Transcriptional repression: the long and the short of it. Genes and Development 15: 2786–2796.

Fulton DL , Sundararajan S , Badis G , et al. (2009) TFCat: the curated catalog of mouse and human transcription factors. Genome Biology 10: R29.

Garvie CW and Wolberger C (2001) Recognition of specific DNA sequences. Molecular Cell 8: 937–946.

Goodman RH and Smolik S (2000) CBP/p300 in cell growth, transformation and development. Genes and Development 14: 1553–1577.

Gross NJ and Barnes PJ (2017) New therapies for asthma and chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine 195: 159–166.

Grossman SR , Engreitz J , Ray JP , et al. (2018) Positional specificity of different transcription factor classes within enhancers. Proceeding of the National Academy of Sciences USA 115: E7222–E7230.

Hantsche M and Cramer P (2017) Conserved RNA polymerase II initiation complex structure. Current Opinion in Structural Biology 47: 17–22.

Hudson WH , Vera IMS , Nwachukwu JC , et al. (2018) Cryptic glucocorticoid receptor‐binding sites pervade genomic NF‐κB response elements. Nature Communications 9: 1337.

Imhof A and Wolffe AP (1998) Transcription: gene control by targeted histone acetylation. Current Biology 8: 422–424.

Ito K , Caramori G , Lim S , et al. (2002) Expression and activity of histone deacetylases in human asthmatic airways. American Journal of Respiratory and Critical Care Medicine 166: 392–396.

Korzus E (2017) Rubinstein‐Taybi syndrome and epigenetic alterations. Advances in Experimental Medicine and Biology 978: 39–62.

Lambert M , Jambon S , Depauw S , et al. (2018a) Targeting transcription factors for cancer treatment. Molecules 23: 1479.

Lambert SA , Jolma A , Campitelli LF , et al. (2018b) The Human transcription factors. Cell 172: 650–665.

Langlais D , Couture C , Balsalobre A , et al. (2012) The Stat3/GR interaction code: predictive value of direct/indirect DNA recruitment for transcription outcome. Molecular Cell 47: 38–49.

Latchman DS (1996a) Transcription factor mutations and disease. New England Journal of Medicine 334: 28–33.

Latchman DS (1996b) Inhibitory transcription factors. International Journal of Biochemistry and Cellular Biology 28: 965–974.

Latchman DS (1999) POU family transcription factors in the nervous system. Journal of Cellular Physiology 179: 126–133.

Latchman DS (2007) Transcription factors. In: eLS. Chichester: John Wiley & Sons Ltd. DOI: 10.1002/9780470015902.a0005278.pub2.

Liu Y , Gong W , Huang CC , et al. (1999) Crystal structure of the conserved core of the herpes simplex virus transcriptional regulatory protein VP16. Genes & Development 13 (13): 1692–1703.

Liu S , Zibetti C , Wan J , Wang G , et al. (2017) Assessing the model transferability for prediction of transcription factor binding sites based on chromatin accessibility. BioMedCentral Bioinformatics 18: 355.

Meyer S , Reverchon S , Nasser W , et al. (2018) Chromosomal organization of transcription: in a nutshell. Current Genetics 64: 555–565.

Niwa H (2018) The principles that govern transcription factor network functions in stem cells. Development 145: 157420.

Papavassiliou K and Papavassiliou AG (2016) Transcription factor drug targets. Journal of Cellular Biochemistry 117: 2693–2696.

Pelham HRB (1982) A regulatory upstream promoter element in the Drosophila hsp70 heat shock gene. Cell 30: 517–528.

Pingault V , Ente D , Dastot‐Le Moal F , et al. (2010) Review and update of mutations causing Waardenburg syndrome. Human Mutation 31: 391–406.

Rogers JM and Bulyk ML (2018) Diversification of transcription factor‐DNA interactions and the evolution of gene regulatory networks. Wiley Interdisciplinary Reviews. Systems Biology and Medicine 25: e1423.

Taniguchi K and Karin M (2018) NF‐κB, inflammation, immunity and cancer: coming of age. Nature Reviews Immunology 18: 309–324.

Tresenrider A and Ünal E (2018) One‐two punch mechanism of gene repression: a fresh perspective on gene regulation. Current Genetics 64: 581–588.

Weikum ER , de Vera IMS , Nwachukwu JC , et al. (2017) Tethering not required: the glucocorticoid receptor binds directly to activator protein‐1 recognition motifs to repress inflammatory genes. Nucleic Acids Research 45: 8596–8608.

Wingender E (2013) Criteria for an updated classification of human transcription factor DNA‐binding domains. Journal of Bioinformatics and Computational 11: 1340007.

Wozniak GG and Strahl BD (2014) Hitting the “mark”:interpreting lysine methylation in the context of active transcription. Biochimica et Biophysica Acta 12: 1353–1361.

Yusuf D , Butland SL , Swanson MI , et al. (2012) The transcription factor encyclopedia. Genome Biology 13: R24.

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. [doi: 10.1002/9780470015902.a0005278.pub3]