Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription

Many cofactors bind the hormone-activated estrogen receptor (ER), yet the s pecific regulators of endogenous ER-mediated gene transcription are unknown . Using chromatin immunoprecipitation (ChIP), we find that ER and a number of coactivators rapidly associate with estrogen responsive promoters follow ing estrogen treatment in a cyclic fashion that is not predicted by current models of hormone activation. Cycles of ER complex assembly are followed b y transcription. In contrast, the anti-estrogen tamoxifen (TAM) recruits co repressors but not coactivators. Using a genetic approach, we show that rec ruitment of the p160 class of coactivators is sufficient for gene activatio n and for the growth stimulatory actions of estrogen in breast cancer suppo rting a model in which ER cofactors play unique roles in estrogen signaling .