Transcriptional complexes engaged by apo-estrogen receptor-α isoforms have divergent outcomes

被引：85

作者：

Métivier, R ^{[1
]}

Penot, G ^{[1
]}

Carmouche, RP ^{[1
]}

Hübner, MR ^{[1
]}

Reid, G ^{[1
]}

Denger, S ^{[1
]}

Manu, D ^{[1
]}

Brand, H ^{[1
]}

Kos, M ^{[1
]}

Benes, V ^{[1
]}

Gannon, F ^{[1
]}

机构：

[1] European Mol Biol Lab, Heidelberg, Germany

来源：

EMBO JOURNAL | 2004年 / 23卷 / 18期

关键词：

ChIP; estrogen receptor; methylation; transcription; unliganded;

D O I：

10.1038/sj.emboj.7600377

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Unliganded (apo-) estrogen receptor alpha (ERalpha, NR3A1) is classically considered as transcriptionally unproductive. Reassessing this paradigm demonstrated that apo- human ERalpha (ERalpha66) and its N-terminally truncated isoform (ERalpha46) are both predominantly nuclear transcription factors that cycle on the endogenous estrogen-responsive pS2 gene promoter in vivo. Importantly, isoform-specific consequences occur in terms of poising the promoter for transcription, as evaluated by determining (i) the engagement of several cofactors and the resulting nucleosomal organization; and (ii) the CpG methylation state of the pS2 promoter. Although transcriptionally unproductive, cycling of apo- ERalpha66 prepares the promoter to respond to ligand, through sequentially targeting chromatin remodeling complexes and general transcription factors. Additionally, apo-ERalpha46 recruits corepressors, following engagement of cofactors identical to those recruited by apo- ERalpha66. Together, these data describe differential activities of ERalpha isoforms. Furthermore, they depict the maintenance of a promoter in a repressed state as a cyclical process that is intrinsically dependent on initial poising of the promoter.

引用

页码：3653 / 3666

页数：14

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