title: Dynamic loss of H2B ubiquitylation without corresponding changes in H3K4 trimethylation during myogenic differentiation.
abstract: Ubiquitylation of H2B on lysine 120 (H2Bub) is associated with active transcriptional elongation. H2Bub has been implicated in histone cross talk and is generally regarded to be a prerequisite for trimethylation of histone 3 lysine 4 (H3K4me3) and H3K79 in both yeast and mammalian cells. We performed a genome-wide analysis of epigenetic marks during muscle differentiation, and strikingly, we observed a near-complete loss of H2Bub in the differentiated state. We examined the basis for global loss of this mark and found that the H2B ubiquitin E3 ligase, RNF20, was depleted from chromatin in differentiated myotubes, indicating that recruitment of this protein to genes substantially decreases upon differentiation. Remarkably, during the course of myogenic differentiation, we observed retention and acquisition of H3K4 trimethylation on a large number of genes in the absence of detectable H2Bub. The Set1 H3K4 trimethylase complex was efficiently recruited to a subset of genes in myotubes in the absence of detectable H2Bub, accounting in part for H3K4 trimethylation in myotubes. Our studies suggest that H3K4me3 deposition in the absence of detectable H2Bub in myotubes is mediated via Set1 and, perhaps, MLL complexes, whose recruitment does not require H2Bub. Thus, muscle cells represent a novel setting in which to explore mechanisms that regulate histone cross talk.
authors.affiliation: Department of Pathology and Cancer Institute, Smilow Research Center, New York University School of Medicine, New York, New York, USA.
authors.forename: Vasupradha
authors.initials: V
authors.lastname: Vethantham
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Christopher
authors.initials: C
authors.lastname: Bowman
authors.forename: Patrik
authors.initials: P
authors.lastname: Asp
authors.forename: Jeong-Heon
authors.initials: JH
authors.lastname: Lee
authors.forename: David G
authors.initials: DG
authors.lastname: Skalnik
authors.forename: Brian D
authors.initials: BD
authors.lastname: Dynlacht
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D015536:Down-Regulation; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000235:genetics* / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism; D035602:Transcriptional Elongation Factors / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D054875:Ubiquitination
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D035602:Transcriptional Elongation Factors; C571258:Wdr82 protein, mouse; C571257:RNF20 protein, mouse; D044767:Ubiquitin-Protein Ligases