Identification of H3K4me1-associated proteins at mammalian enhancers

哺乳动物增强子中 H3K4me1 相关蛋白的鉴定

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作者:Andrea Local #, Hui Huang #, Claudio P Albuquerque, Namit Singh, Ah Young Lee, Wei Wang, Chaochen Wang, Judy E Hsia, Andrew K Shiau, Kai Ge, Kevin D Corbett, Dong Wang, Huilin Zhou, Bing Ren

Abstract

Enhancers act to regulate cell-type-specific gene expression by facilitating the transcription of target genes. In mammalian cells, active or primed enhancers are commonly marked by monomethylation of histone H3 at lysine 4 (H3K4me1) in a cell-type-specific manner. Whether and how this histone modification regulates enhancer-dependent transcription programs in mammals is unclear. In this study, we conducted SILAC mass spectrometry experiments with mononucleosomes and identified multiple H3K4me1-associated proteins, including many involved in chromatin remodeling. We demonstrate that H3K4me1 augments association of the chromatin-remodeling complex BAF to enhancers in vivo and that, in vitro, H3K4me1-marked nucleosomes are more efficiently remodeled by the BAF complex. Crystal structures of the BAF component BAF45C indicate that monomethylation, but not trimethylation, is accommodated by BAF45C's H3K4-binding site. Our results suggest that H3K4me1 has an active role at enhancers by facilitating binding of the BAF complex and possibly other chromatin regulators.

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