Transcriptional complexes engaged by apo-estrogen receptor-alpha isoforms have divergent outcomes.
EMBO J
; 23(18): 3653-66, 2004 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-15343269
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Apoproteínas
/
Transcrição Gênica
/
Regiões Promotoras Genéticas
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Receptor alfa de Estrogênio
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Proteínas de Membrana
Limite:
Humans
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Alemanha