A transcriptional switch mediated by cofactor methylation.
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Xu W, Chen H, Du K, Asahara H, Tini M, Emerson BM, Montminy M, Evans RM
A transcriptional switch mediated by cofactor methylation.
Science. 2001 Dec 21;294(5551):2507-11. doi: 10.1126/science.1065961. Epub 2001 Nov 8.
- PubMed ID
- 11701890 [ View in PubMed]
- 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.