Identification of H3K4me1-associated proteins at mammalian enhancers

Autor: Claudio P. Albuquerque, Andrew K. Shiau, Hui Huang, Kai Ge, Kevin D. Corbett, Huilin Zhou, Andrea Local, Namit Singh, Wei Wang, Ah Young Lee, Dong Wang, Chaochen Wang, Judy E. Hsia, Bing Ren
Rok vydání: 2017
Předmět:
Zdroj: Nature Genetics. 50:73-82
ISSN: 1546-1718
1061-4036
DOI: 10.1038/s41588-017-0015-6
Popis: 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.
Databáze: OpenAIRE