A role for H3K4 monomethylation in gene repression and partitioning of chromatin readers

Jemmie Cheng, Roy Blum, Christopher Bowman, Deqing Hu, Ali Shilatifard, Steven Shen, Brian D. Dynlacht*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

123 Scopus citations

Abstract

Monomethylation of lysine 4 on histone H3 (H3K4me1) is a well-established feature of enhancers and promoters, although its function is unknown. Here, we uncover roles for H3K4me1 in diverse cell types. Remarkably, we find that MLL3/4 provokes monomethylation of promoter regions and the conditional repression of muscle and inflammatory response genes in myoblasts. During myogenesis, muscle genes are activated, lose MLL3 occupancy, and become H3K4-trimethylated through an alternative COMPASS complex. Monomethylation-mediated repression was not restricted to skeletal muscle. Together with H3K27me3 and H4K20me1, H3K4me1 was associated with transcriptional silencing in embryonic fibroblasts, macrophages, and human embryonic stem cells (ESCs). On promoters of active genes, we find that H3K4me1 spatially demarcates the recruitment of factors that interact with H3K4me3, including ING1, which, in turn, recruits Sin3A. Our findings point to a unique role for H3K4 monomethylation in establishing boundaries that restrict the recruitment of chromatin-modifying enzymes to defined regions within promoters.

Original languageEnglish (US)
Pages (from-to)979-992
Number of pages14
JournalMolecular cell
Volume53
Issue number6
DOIs
StatePublished - Mar 20 2014

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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