Transcriptional Gene Regulation in Eukaryotes

Abstract

Regulation of gene transcription is the primary means by which gene expression is controlled to produce different proteins in different cell types or in response to different stimuli. This process is controlled by transcription factors that belong to specific families which are defined on the basis of the different protein domains used to bind to deoxyribonucleic acid (DNA). Many transcription factors contain specific activation domains which allow them to activate transcription. In contrast, other transcription factors repress transcription either directly or indirectly by interfering with positively acting factors. Moreover, DNA‐binding transcription factors can also interact with one another and with non‐DNA‐binding coactivators and corepressors so allowing an individual transcription factor to differentialy regulate different genes. In turn, transcription factors are themselves regulated by controlling either their synthesis or by activating them from a pre‐existing inactive state by mechanisms such as ligand binding, phosphorylation or dissociation of an inhibitory protein. These mechanisms allow cellular differentiation events or specific signals to regulate gene expression by altering the synthesis and/or activity of individual transcription factors and thereby altering the expression of their target genes.

Key Concepts:

  • Regulation of the transcription of DNA into RNA is the key event controlling gene expression.

  • Transcription is regulated by specific proteins called transcription factors.

  • Many of these factors act by binding to specific DNA sequences in gene promoters or enhancers.

  • Transcription factors bind to the DNA via specific DNA‐binding domains which differ between different transcription factor families.

  • Following DNA binding, some factors activate transcription via specific activation domains.

  • Other transcription factors can repress transcription either directly or indirectly by interfering with the action of positively acting factors.

  • In order to regulate gene transcription, transcription factors are themselves regulated by controlling either their synthesis or their activity.

  • The rate of transcription of a particular gene is therefore determined by the balance between the levels/activity of the activating and inhibitory transcription factors which act on it.

Keywords: transcriptional control; transcription factor; gene activation; gene repression; promoter; Enhancer

Figure 1.

Structure of a typical eukaryotic gene with a TATA box‐containing promoter, upstream promoter elements (UPEs) such as the CCAAT and Sp1 boxes, regulatory elements inducing expression in specific cell types or in response to specific treatments such as cAMP (CRE) or glucocorticoid hormones (GRE) and other elements within more distant enhancers. Note that, as discussed in the text, UPEs are often interdigitated with regulatory elements, and the same regulatory elements can be found both upstream from the promoter and in enhancers.

Figure 2.

Mechanisms by which an inhibitory factor (R) can repress transcription. These involve inhibiting an activator (A) binding to its binding site (ABS) in the DNA, by producing an inactive chromatin structure (a), by competing for the DNA‐binding site (b), or by sequestering the activator in solution (c), inhibiting the ability of DNA‐bound activator to stimulate transcription (d) or direct repression (e).

Figure 3.

Mechanisms by which transcription factors can be activated from an inactive (square) to an active (circle) form by post‐translational changes: factor activated by (a) binding to ligand; (b) dissociation of an inhibitor protein; (c) protein modification.

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References

Brand M, Leurent C, Mallouh V, Tora L and Schultz P (1999) Three‐dimensional structures of the TAFII‐containing complexes TFIID and TFTC. Science 286: 2151–2153.

Chrivia JC, Kwok RP, Lamb N et al. (1993) Phosphorylated CBEB binds specifically to the nuclear protein CBP. Nature 365: 855–859.

Davis HL, Wentraub H and Lassar AB (1987) Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell 51: 987–1000.

Grosschedl R and Birnsteil ML (1980) Spacer DNA sequences up‐stream of the TATAAATA sequence are essential for promotion of histone H2A transcription in vivo. Proceedings of the National Academy of Sciences of the USA 77: 7102–7106.

Miller J, McLachlan AD and Klug A (1985) Repetitive zinc‐binding domains in the protein transcription factor III A from Xenopus oocytes. EMBO Journal 4: 1609–1614.

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

Schwabe JWR and Rhodes D (1991) Beyond zinc fingers: steroid hormone receptors have a novel structural motif for DNA recognition. Trends in Biochemical Sciences 16: 291–296.

Further Reading

Charoensawan V, Wilson D and Teichmann SA (2010) Lineage‐specific expansion of DNA‐binding transcription factor families. Trends in Genetics 26: 388–393.

D'Alessio JA, Wright KJ and Tijian R (2009) Shifting players and paradigms in cell‐specific transcription. Molecular Cell 36: 924–931.

Dahan O, Gingold H and Pilpel Y (2011) Regulatory mechanisms and networks couple the different phases of gene expression. Trends in Genetics 27: 316–322.

Latchman DS (2008) Eukaryotic Transcription Factors, 5th edn. New York, London: Elsevier, Academic Press.

Latchman DS (2010) Gene Control Gene Regulation, 6th edn. New York, London: Garland Science.

Ong CT and Corces VG (2011) Enhancer function: new insights into the regulation of tissue‐specific gene expression. Nature Reviews Genetics 12: 283–293.

Pan Y, Tsai CJ, Ma B and Nussinov R (2010) Mechanisms of transcription factor selectivity. Trends in Genetics 26: 75–83.

Perissi V, Jepsen K, Glass CK and Rosenfeld MG (2010) Deconstructing repression: evolving models of co‐repressor action. Nature Reviews Genetics 11: 109–123.

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How to Cite close
Latchman, David S(Nov 2011) Transcriptional Gene Regulation in Eukaryotes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0002322.pub2]