Two Chromatin Remodeling Activities Cooperate during Activation of Hormone Responsive Promoters

Abstract

Steroid hormones regulate gene expression by interaction of their receptors with hormone responsive elements (HREs) and recruitment of kinases, chromatin remodeling complexes, and coregulators to their target promoters. Here we show that in breast cancer cells the BAF, but not the closely related PBAF complex, is required for progesterone induction of several target genes including MMTV, where it catalyzes localized displacement of histones H2A and H2B and subsequent NF1 binding. PCAF is also needed for induction of progesterone target genes and acetylates histone H3 at K14, an epigenetic mark that interacts with the BAF subunits by anchoring the complex to chromatin. In the absence of PCAF, full loading of target promoters with hormone receptors and BAF is precluded, and induction is compromised. Thus, activation of hormone-responsive promoters requires cooperation of at least two chromatin remodeling activities, BAF and PCAF.

More help than hindrance

“…2 Following H1 displacement, hormone treatment leads to recruitment of the ATP-dependent remodeling complex BAF, which catalyzes displacement of core histones H2A and H2B from the MMTV promoter. 8,10 Consistently we find a significant recruitment of the Brg1 subunit of BAF as well as H2A/H2B displacement in PRbs with high NRI but not in low NRI PRbs. Eviction of H1 and/or H2A/H2B dimers destabilizes the nucleosome particle leading to internal cleavage of nucleosomal DNA by MNase and consequent reduction of nucleosomal DNA fragments.…”

“…Remodeling is at least in part mediated by the ATPdependent complexes NURF and BAF, which remove histones H1 and histone H2A/H2B dimers, respectively. Thus, mechanisms of remodeling previously observed in the MMTV promoter 6,8,10,22 are representative of a genome-wide behavior. We hypothesize that removal of histone H1 may be the main mechanism for initiating cooperative decondensation of the chromatin fiber, though we cannot exclude that different histone H1 isoforms are also involved and the extent of histones or DNA methylation play also a role.…”

“…1). 10 We have previously demonstrated that local displacement of histones H1 and H2A/ H2B are needed for optimal induction of the MMTV promoter and other progestin-target genes. Thus, crosstalk of PR with kinase signaling pathways, histone modifying enzymes and ATP-dependent complexes impinges on chromatin that is remodeled in two consecutive cycles as a requisite for gene regulation.…”

“…8,9 (C) In a subsequent step BAF catalyzes histone H2A/H2B displacement. 10 (D) After chromatin remodeling, PR interacts with other TFs, co-regulators and components of the transcriptional machinery, to promote formation of the transcription initiation complex.…”

Vitamin A and retinoid signaling: genomic and nongenomic effects

“…According to several reports ( 96,142,143 ), histone phosphorylation would contribute to transcription as a chromatin mark accounting for, in cooperation with other histone modifi cations, chromatin remodeling and promoter recruitment of RXR/RAR heterodimers and the transcriptional machinery ( Fig. 6 ).…”