title: The oncogenic polycomb histone methyltransferase EZH2 methylates lysine 120 on histone H2B and competes ubiquitination.
abstract: The histone methyltransferase enhancer of zeste 2 (EZH2) is known to be a polycomb protein homologous to Drosophila enhancer of zeste and catalyzes the addition of methyl groups to histone H3 at lysine 27 (H3K27). We previously reported that EZH2 was overexpressed in various types of cancer and plays a crucial role in the cell cycle regulation of cancer cells. In the present study, we demonstrated that EZH2 has the function to monomethylate lysine 120 on histone H2B (H2BK120). EZH2-dependent H2BK120 methylation in cancer cells was confirmed with an H2BK120 methylation-specific antibody. Overexpression of EZH2 significantly attenuated the ubiquitination of H2BK120, a key posttranslational modification of histones for transcriptional regulation. Concordantly, knockdown of EZH2 increased the ubiquitination level of H2BK120, suggesting that the methylation of H2BK120 by EZH2 may competitively inhibit the ubiquitination of H2BK120. Subsequent chromatin immunoprecipitation-Seq and microarray analyses identified downstream candidate genes regulated by EZH2 through the methylation of H2BK120. This is the first report to describe a novel substrate of EZH2, H2BK120, unveiling a new aspect of EZH2 functions in human carcinogenesis.
authors: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan ; Department of Surgery, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors: Masaharu
authors: M
authors: Kogure
authors: Masashi
authors: M
authors: Takawa
authors: Vassiliki
authors: V
authors: Saloura
authors: Kenbun
authors: K
authors: Sone
authors: Lianhua
authors: L
authors: Piao
authors: Koji
authors: K
authors: Ueda
authors: Reem
authors: R
authors: Ibrahim
authors: Tatsuhiko
authors: T
authors: Tsunoda
authors: Masanori
authors: M
authors: Sugiyama
authors: Yutaka
authors: Y
authors: Atomi
authors: Yusuke
authors: Y
authors: Nakamura
authors: Ryuji
authors: R
authors: Hamamoto
mesh_terms: D063646:Carcinogenesis; D002460:Cell Line; D045744:Cell Line, Tumor; D000071221:Enhancer of Zeste Homolog 2 Protein; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D057809:HEK293 Cells; D006367:HeLa Cells; D006657:Histones / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000235:genetics* / Q000378:metabolism; D061986:MCF-7 Cells; D063151:Polycomb Repressive Complex 2 / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic; D054875:Ubiquitination
chemical_list: D006657:Histones; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D008239:Lysine