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Ceschin D.G.,Institute Genetique Of Biologie Mole Culaire Et Cellulaire Igbmc | Walia M.,Institute Genetique Of Biologie Mole Culaire Et Cellulaire Igbmc | Wenk S.S.,Institute Genetique Of Biologie Mole Culaire Et Cellulaire Igbmc | Duboe C.,University Paul Sabatier | And 10 more authors.
Genes and Development | Year: 2011

Multiple signaling pathways ultimately modulate the epigenetic information embedded in the chromatin of gene promoters by recruiting epigenetic enzymes. We found that, in estrogen-regulated gene programming, the acetyltransferase CREB-binding protein (CBP) is specifically and exclusively methylated by the coactivatorassociated arginine methyltransferase (CARM1) in vivo. CARM1-dependent CBP methylation and p160 coactivators were required for estrogen-induced recruitment to chromatin targets. Notably, methylation increased the histone acetyltransferase (HAT) activity of CBP and stimulated its autoacetylation. Comparative genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) studies revealed a variety of patterns by which p160, CBP, and methyl-CBP (meCBP) are recruited (or not) by estrogen to chromatin targets. Moreover, significant target gene-specific variation in the recruitment of (1) the p160 RAC3 protein, (2) the fraction of a given meCBP species within the total CBP, and (3) the relative recruitment of different meCBP species suggests the existence of a target gene-specific ''fingerprint'' for coregulator recruitment. Crossing ChIP-seq and transcriptomics profiles revealed the existence of meCBP ''hubs'' within the network of estrogen-regulated genes. Together, our data provide evidence for an unprecedented mechanism by which CARM1-dependent CBP methylation results in geneselective association of estrogen-recruited meCBP species with different HAT activities and specifies distinct target gene hubs, thus diversifying estrogen receptor programming. © 2011 by Cold Spring Harbor Laboratory Press.

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