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) (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.



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Further Reading

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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]