title: Histone H2A ubiquitination inhibits the enzymatic activity of H3 lysine 36 methyltransferases.
abstract: Histone H3 lysine 27 (H3K27) methylation and H2A monoubiquitination (ubH2A) are two closely related histone modifications that regulate Polycomb silencing. Previous studies reported that H3K27 trimethylation (H3K27me3) rarely coexists with H3K36 di- or tri-methylation (H3K36me2/3) on the same histone H3 tails, which is partially controlled by the direct inhibition of the enzymatic activity of H3K27-specific methyltransferase PRC2. By contrast, H3K27 methylation does not affect the catalytic activity of H3K36-specific methyltransferases, suggesting other Polycomb mechanism(s) may negatively regulate the H3K36-specific methyltransferase(s). In this study, we established a simple protocol to purify milligram quantities of ubH2A from mammalian cells, which were used to reconstitute nucleosome substrates with fully ubiquitinated H2A. A number of histone methyltransferases were then tested on these nucleosome substrates. Notably, all of the H3K36-specific methyltransferases, including ASH1L, HYPB, NSD1, and NSD2 were inhibited by ubH2A, whereas the other histone methyltransferases, including PRC2, G9a, and Pr-Set7 were not affected by ubH2A. Together with previous reports, these findings collectively explain the mutual repulsion of H3K36me2/3 and Polycomb modifications.
authors.affiliation: From the College of Life Sciences, Beijing Normal University, Beijing, 100875.
authors.forename: Gang
authors.initials: G
authors.lastname: Yuan
authors.forename: Ben
authors.initials: B
authors.lastname: Ma
authors.forename: Wen
authors.initials: W
authors.lastname: Yuan
authors.forename: Zhuqiang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Ding
authors.forename: Li
authors.initials: L
authors.lastname: Feng
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Shen
authors.forename: She
authors.initials: S
authors.lastname: Chen
authors.forename: Guohong
authors.initials: G
authors.lastname: Li
authors.forename: Bing
authors.initials: B
authors.lastname: Zhu
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008745:Methylation; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D000076983:Histone Methyltransferases; C490911:ASH1L protein, human; D011495:Histone-Lysine N-Methyltransferase; C113272:NSD1 protein, human; C491867:Nsd1 protein, mouse
keywords: Chromatin; Chromatin Histone Modification; Histone Methylation; Transcription Regulation; Ubiquitination
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