A role for H3K4 mono-methylation in facultative heterochromatin assembly and partitioning of chromatin readers

Mono-methylation of lysine 4 on histone H3 (H3K4me1) is a well-established feature of enhancers and promoters, although its function is unknown. Remarkably, we find H3K4me1 at the promoter regions of conditionaly-repressed muscle and stimulus-dependent inflammatory response genes in myoblasts. During myogenesis, muscle genes are activated and become H3K4-trimethylated. On the promoters of active genes, we find that H3K4me1 spatially restricts the recruitment of “readers” of H3K4me3, including ING1, which, in turn, recruits Sin3A. Our findings point to a unique role for H3K4 mono-methylation in establishing boundaries that restrict the recruitment of chromatin-modifying enzymes to defined regions within promoters. Overall design: Mapping of Wdr5, Menin, MLL1, Sin3A, and LSD1 in growing myoblasts (MB) and ING1 in growing myoblasts (MB) and fully differentiated myotubes (MT).