Identification of H3K4me1-associated proteins at mammalian enhancers

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-spec experiments with mono-nucleosomes and identified multiple H3K4me1 associated proteins, including many involved in chromatin remodeling. We demonstrate that H3K4me1 augments the association of the chromatin remodeling complex BAF to enhancers in vivo and that in vitro, H3K4me1 nucleosomes are more efficiently remodeled by the BAF complex. Crystal structures of BAF component BAF45c reveal that monomethylation, but not trimethylation, is accommodated by BAF45c’s H3K4 binding site. Our results suggest that H3K4me1 plays an active role at enhancers by facilitating the binding of the BAF complex and possibly other chromatin regulators.

17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes

“…As we did not observe consistent associations between PSP-associated MAPT intron 1 variants with either LRRC37A/2 copy number and expression, or MAPT expression and splicing, we examined ATAC-seq data and publicly available epigenetic data in order to determine the likely functional impact of rs8076152 and H1c variants. Analysis of publicly available ChIP-seq data (Roadmap Epigenetics Consortium 47 ) reveals that rs242557 lies within a region enriched for H3K27ac, H3K4me1and H3K9ac marks in brain tissue (Fig 5A, SI Table 10), which is consistent with the presence of an active enhancer region in this locus [48][49][50] . The second PSP-associated variant, rs8076152, is also within a brain-specific weak enhancer region (Fig 5A, SI Table 10).…”

Linking aberrant chromatin features in chronic lymphocytic leukemia to transcription factor networks

“…While little is known about the function of remodeling complexes in CLL, the NuRD and SWI/SNF remodelers play an important role in hematopoiesis and differentiation and have been implicated in oncogenesis and cancer progression in numerous other entities (Lai & Wade, ; Kadoch & Crabtree, ; Prasad et al , ). Furthermore, it is noted that the ability of these complexes to translocate nucleosomes might be crucial to modulate chromatin accessibility at enhancers and involve their targeting by histone modifications like H3K4me1 (Local et al , ). In line with these considerations, we observe striking changes in nucleosome positioning and occupancy at B‐cell‐specific genes in CLL.…”

H3.3K4M destabilizes enhancer epigenomic writers MLL3/4 and impairs adipose tissue development

“…Although H3K4me1 is the predominant mark of a primed enhancer state, it is unclear whether H3K4me1 affects or simply correlates with enhancer activation in cell differentiation and development. Interestingly, the latest two studies from one group reported that MLL3/4-dependent H3K4me1 has an active role at enhancers by facilitating binding of the chromatin remodeler SWI/SNF complex and recruitment of the chromatin organization regulator cohesin complex to orchestrate long-range chromatin interactions in ES cells 20,21 . These findings imply that H3K4me1 is not simply a correlative outcome in enhancer regulation.…”