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

doi:10.1016/j.molcel.2014.02.032

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

Mol Cell. 2014 Mar 20;53(6):979-92. doi: 10.1016/j.molcel.2014.02.032.

Authors

Jemmie Cheng¹, Roy Blum¹, Christopher Bowman¹, Deqing Hu², Ali Shilatifard², Steven Shen³, Brian D Dynlacht⁴

Affiliations

¹ Department of Pathology and Cancer Institute, Smilow Research Center, New York University School of Medicine, New York, NY 10016, USA.
² Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
³ GTC, Department of Biochemistry and Molecular Pharmacology, NYU School of Medicine, New York, NY 10016, USA.
⁴ Department of Pathology and Cancer Institute, Smilow Research Center, New York University School of Medicine, New York, NY 10016, USA. Electronic address: [email protected].

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.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Chromatin*
DNA Methylation
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism
Embryo, Mammalian
Embryonic Stem Cells / cytology
Embryonic Stem Cells / metabolism
Enhancer Elements, Genetic
Fibroblasts / cytology
Fibroblasts / metabolism
Gene Expression Regulation, Developmental*
Genome
Histone-Lysine N-Methyltransferase
Histones / genetics*
Histones / metabolism
Humans
Inhibitor of Growth Protein 1
Intracellular Signaling Peptides and Proteins / genetics
Intracellular Signaling Peptides and Proteins / metabolism
Macrophages / cytology
Macrophages / metabolism
Mice
Muscle Development / genetics*
Myoblasts / cytology
Myoblasts / metabolism*
Nuclear Proteins / genetics
Nuclear Proteins / metabolism
Promoter Regions, Genetic
Repressor Proteins / genetics
Repressor Proteins / metabolism
Signal Transduction
Sin3 Histone Deacetylase and Corepressor Complex
Tumor Suppressor Proteins / genetics
Tumor Suppressor Proteins / metabolism

Substances

Chromatin
DNA-Binding Proteins
Histones
ING1 protein, human
Inhibitor of Growth Protein 1
Intracellular Signaling Peptides and Proteins
KMT2C protein, human
Nuclear Proteins
Repressor Proteins
SIN3A transcription factor
Tumor Suppressor Proteins
Histone-Lysine N-Methyltransferase
MLL4 protein, human
Sin3 Histone Deacetylase and Corepressor Complex

Associated data

GEO/GSE50590

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding