Publication Date:
2001-11-10
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, W -- Chen, H -- Du, K -- Asahara, H -- Tini, M -- Emerson, B M -- Montminy, M -- Evans, R M -- 9R01DK57978/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2001 Dec 21;294(5551):2507-11. Epub 2001 Nov 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gene Expression Laboratory, Department of Biological Chemistry, University of California Davis Cancer Center/Basic Science, Sacramento, CA 95817, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11701890" target="_blank"〉PubMed〈/a〉
Keywords:
Acetyltransferases/metabolism
;
Amino Acid Sequence
;
Animals
;
Apoptosis
;
Cell Line
;
Cyclic AMP Response Element-Binding Protein/metabolism
;
Dimerization
;
E1A-Associated p300 Protein
;
*Gene Expression Regulation
;
Genes, Reporter
;
Histone Acetyltransferases
;
Histones/metabolism
;
Methylation
;
Molecular Sequence Data
;
Nerve Growth Factor/pharmacology
;
Nuclear Proteins/chemistry/*metabolism
;
PC12 Cells
;
Protein Structure, Tertiary
;
Protein-Arginine N-Methyltransferases/*metabolism
;
Rats
;
Receptors, Retinoic Acid/*metabolism
;
Recombinant Fusion Proteins/metabolism
;
Retinoid X Receptors
;
*Saccharomyces cerevisiae Proteins
;
Signal Transduction
;
Somatostatin/genetics
;
Trans-Activators/chemistry/*metabolism
;
Transcription Factors/metabolism
;
*Transcription, Genetic
;
Transcriptional Activation
;
Transfection
;
Tretinoin/metabolism/pharmacology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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