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Chromatin Regulates CREB Phosphorylation

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Science  03 Mar 2000:
Vol. 287, Issue 5458, pp. 1557
DOI: 10.1126/science.287.5458.1557g

Chromatin structure influences the transcriptional activity of genes by regulating promoter accessibility to transcription factors and, as Michael et al. discuss, by regulating the transcription factors themselves. Cyclic AMP-regulated enhancer binding protein (CREB) is a transcription factor that is phosphorylated by the cyclic AMP protein kinase; this step leads to a transient burst in transcriptional activation followed by an attenuation phase as CREB is dephosphorylated. The CREB coactivator proteins CREB-binding protein (CBP) and p300 both possess histone acetyltransferase activity, which induces changes in chromatin structure and allows productive assembly of the transcriptional apparatus onto the target promoter. Michael et al. show that the phosphorylation of CREB and transcription of cAMP-responsive genes can be potentiated by inhibitors of histone deacetylase. Histone deacetylase inhibitors prolonged the length of time that CREB remained phosphorylated, which suggests a chromatin-dependent mechanism for transcriptional attenuation and the influence of promoter-bound nucleosomes on the accessibility of the protein kinase to CREB.—NG

Mol. Cell. Biol.20, 1596 (2000).

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