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.
Highlights
Regulation of eukaryotic gene expression implies mechanisms that permit transcription factors to gain access to chromatin packaged DNA sequences
In order to adapt its gene expression program to the needs of the environment, the cell must access the information stored in the DNA sequence that is tightly packaged into chromatin in the cell nucleus
In breast cancer cells treated with the ovarian hormone progesterone, the hormone receptor recruits to the regulated genes two chromatin remodeling complexes that cooperate in opening the chromatin structure
Summary
Regulation of eukaryotic gene expression implies mechanisms that permit transcription factors to gain access to chromatin packaged DNA sequences. Modulation of the structure and dynamics of nucleosomes is an important regulatory mechanism in all DNA-based processes and is catalyzed by chromatin remodeling complexes. Such complexes can either modify histone residues or use the energy of ATP hydrolysis to alter the relationship between histones and DNA [2,3]. The yeast SWI/SNF complex, the first ATP-dependent chromatin remodeling complex to be identified, is a 2-MDa complex of 11 subunits that regulates gene expression by catalyzing octamer transfer, nucleosome sliding, dinucleosome formation, and H2A/H2B displacement [4,5,6]. BAF57 has been reported as a common subunit for BAF and PBAF complexes [4,9]
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