A transcriptional switch mediated by cofactor methylation

W. Xu, Hongwu Chen, K. Du, H. Asahara, M. Tini, B. M. Emerson, M. Montminy, R. H. Evans

Research output: Contribution to journalArticlepeer-review

325 Scopus citations

Abstract

We describe a molecular switch based on the controlled methylation of nucleosome and the transcriptional cofactors, the CREB-binding proteins (CBP)/p300. The CBP/p300 methylation site is localized to an arginine residue that is essential for stabilizing the structure of the KIX domain, which mediates CREB recruitment. Methylation of KIX by coactivator-associated arginine methyltransferase 1 (CARM1) blocks CREB activation by disabling the interaction between KIX and the kinase inducible domain (KID) of CREB. Thus, CARM1 functions as a corepressor in cyclic adenosine monophosphate signaling pathway via its methyltransferase activity while acting as a coactivator for nuclear hormones. These results provide strong in vivo and in vitro evidence that histone methylation plays a key role in hormone-induced gene activation and define cofactor methylation as a new regulatory mechanism in hormone signaling.

Original languageEnglish (US)
Pages (from-to)2507-2511
Number of pages5
JournalScience
Volume294
Issue number5551
DOIs
StatePublished - Dec 21 2001

ASJC Scopus subject areas

  • General

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