Transcriptional Regulation: Coordination


In higher eukaryotes, gene expression is tightly coordinated at multiple stages with other events that orchestrate the life of the cell. Prompted by an initial signal, regulatory transcription factors are activated, assemble at specific enhancer sequences and trigger a cascade of reactions, resulting in an appropriately remodeled chromatin template, with functional transcription machinery on the promoter. Phosphorylation, acetylation and methylation orchestrate the interconnection of the different steps.

Keywords: transcription; initiation; activators; chromatin; phosphorylation

Figure 1.

Model for activation of gene transcription. (a) Activators bind to their DNA‐specific recognition sequences in a context of repressive chromatin; (b) once turned on, activators recruit a battery of coregulators acting in a coordinated manner to decompact chromatin: (i) ATP‐dependent remodeling complexes (SWI/SNF) which displace the impeding nucleosomes; (ii) histone acetyltransferase (HAT) complexes associated with histone methyltransferases (HMTs) and histone kinases which acetylate, methylate and phosphorylate histones, thus changing histone–DNA and histone–histone contacts. Each coregulator can also modify activators as well as the other coregulators, enhancing and/or disrupting the interactions between activators and coregulators. The efficiency of these events is increased by phosphorylation processes in response to physiological or environmental signals; (c) activators recruit the mediator complex which will expedite entry of RNA polymerase II (RNA pol II) and general transcription factors into the preinitiation complex. At this step, the Cdk7 subunit of transcription factor IIH (TFIIH) can phosphorylate certain activators, increasing the efficiency of the transcription initiation complex assembly. Cdk7 also phosphorylates the RNA pol II (PRNA pol II) C‐terminal domain (CTD), favoring the transition from the initiation to the elongation phase. At this step, phosphorylation processes in response to specific signals would negatively regulate activated transcription by inactivating activators or targeting the CTD. Ac: acetylation; P: phosphate; TAFIIs: transcription associated factors; TBP: TATA‐binding protein; SWI: mating type switching; SNF: sucrose nonfermenting.



Akoulitchev S, Chuikov S and Reinberg D (2000) TFIIH is negatively regulated by Cdk8‐containing mediator complexes. Nature 407: 102–106.

Brivanlou AH and Darnell Jr JE (2002) Signal transduction and the control of gene expression. Science 295: 813–818.

Egly JM (2001) The 14th Datta Lecture. TFIIH: from transcription to clinic. FEBS Letters 498: 124–128.

Gianni M, Bauer A, Garattini E, Chambon P and Rochette‐Egly C (2002) Phosphorylation by p38MAPK and recruitment of SUG‐1 are required for RA‐induced RARγ degradation and transactivation. EMBO Journal 21: 3760–3769.

Hunter T (2000) Signaling – 2000 and beyond. Cell 100: 113–127.

Jiang YW, Veschambre P, Erdjument‐Bromage H, et al. (1998) Mammalian mediator of transcriptional regulation and its possible role as an end‐point of signal transduction pathways. Proceedings of the National Academy of Sciences of the United States of America 95: 8538–8543.

Keriel A, Stary A, Sarasin A, Rochette‐Egly C and Egly JM (2002) XPD mutations prevent TFIIH‐dependent transactivation by nuclear receptors and phosphorylation of RARalpha. Cell 109: 125–135.

Klochendler‐Yeivin A, Muchardt C and Yaniv M (2002) SWI/SNF chromatin remodeling and cancer. Current Opinion in Genetics and Development 12: 73–79.

Malik S and Roeder RG (2000) Transcriptional regulation through mediator‐like coactivators in yeast and metazoan cells. Trends in Biochemical Sciences 25: 277–283.

Narlikar GJ, Fan HY and Kingston RE (2002) Cooperation between complexes that regulate chromatin structure and transcription. Cell 108: 475–487.

Orphanides G and Reinberg D (2002) A unified theory of gene expression. Cell 108: 439–451.

Proudfoot NJ, Furger A and Dye MJ (2002) Integrating mRNA processing with transcription. Cell 108: 501–512.

Woychik NA and Hampsey M (2002) The RNA polymerase II machinery: structure illuminates function. Cell 108: 453–463.

Further Reading

Agalioti T, Lomvardas S, Parekh B, et al. (2000) Ordered recruitment of chromatin modifying and general transcription factors to the IFN‐beta promoter. Cell 103: 667–678.

Cheung P, Allis CD and Sassone‐Corsi P (2000) Signaling to chromatin through histone modifications. Cell 103: 263–271.

Cosma MP (2002) Ordered recruitment: gene specific mechanism of transcription activation. Molecular Cell 10: 227–236.

Dilworth FJ and Chambon P (2001) Nuclear receptors coordinate the activities of chromatin remodeling complexes and coactivators to facilitate initiation of transcription. Oncogene 20: 3047–3054.

Featherstone M (2002) Coactivators in transcription initiation: here are your orders. Current Opinion in Genetics and Development 12: 149–155.

Kouzarides T (2002) Histone methylation in transcriptional control. Current Opinion in Genetics and Development 12: 198–209.

Krebs JE, Kuo MH, Allis CD and Peterson CL (1999) Cell cycle‐regulated histone acetylation required for expression of the yeast HO gene. Genes and Development 13: 1412–1421.

Riedl T and Egly JM (2000) Phosphorylation in transcription: the CTD and more. Gene Expression 9: 3–13.

Shang Y, Myers M and Brown M (2002) Formation of the androgen receptor transcription complex. Molecular Cell 9: 601–610.

Thomas D and Tyers M (2000) Transcriptional regulation: kamikaze activators. Current Biology 10: 341–343.

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Egly, Jean‐Marc, and Rochette‐Egly, Cécile(Sep 2005) Transcriptional Regulation: Coordination. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0005288]