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Nat Genet. 2018 Jan;50(1):73-82. doi: 10.1038/s41588-017-0015-6. Epub 2017 Dec 18.

Identification of H3K4me1-associated proteins at mammalian enhancers.

Author information

1
Ludwig Institute for Cancer Research, La Jolla, CA, USA.
2
Aptose Biosciences, Inc., San Diego, CA, USA.
3
Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA, USA.
4
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA.
5
National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of Health, Bethesda, MD, USA.
6
Department of Cellular and Molecular Medicine, University of California San Diego School of Medicine, La Jolla, CA, USA.
7
Ludwig Institute for Cancer Research, La Jolla, CA, USA. biren@ucsd.edu.
8
Department of Cellular and Molecular Medicine, University of California San Diego School of Medicine, La Jolla, CA, USA. biren@ucsd.edu.
9
Center for Epigenomics, Institute of Genomic Medicine, La Jolla, CA, USA. biren@ucsd.edu.

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.

PMID:
29255264
PMCID:
PMC6007000
DOI:
10.1038/s41588-017-0015-6
[Indexed for MEDLINE]
Free PMC Article

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