モチヅキ　マキコ   望月　牧子    所属   医学部 医学科    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Ezh1 Targets Bivalent Genes to Maintain Self-Renewing Stem Cells in Ezh2-Insufficient Myelodysplastic Syndrome.
掲載誌名	正式名：iScience 略　 称：iScience ISSNコード：25890042/25890042
掲載区分	国外
巻・号・頁	9,pp.161-174
著者・共著者	Aoyama Kazumasa, Oshima Motohiko, Koide Shuhei, Suzuki Emi, Mochizuki-Kashio Makiko, Kato Yuko, Tara Shiro, Shinoda Daisuke, Hiura Nobuhiro, Nakajima-Takagi Yaeko, Sashida Goro, Iwama Atsushi
発行年月	2018/11
概要	Polycomb repressive complex (PRC) 2 represses transcription through histone H3K27 trimethylation (H3K27me3). We previously reported that the hematopoietic-cell-specific deletion of Ezh2, encoding a PRC2 enzyme, induced myelodysplastic syndrome (MDS) in mice, whereas the concurrent Ezh1 deletion depleted hematopoietic stem and progenitor cells (HSPCs). We herein demonstrated that mice with only one Ezh1 allele (Ezh1+/-Ezh2Δ/Δ) maintained HSPCs. A chromatin immunopreciptation sequence analysis revealed that residual PRC2 preferentially targeted genes with high levels of H3K27me3 and H2AK119 monoubiquitination (H2AK119ub1) in HSPCs (designated as Ezh1 core target genes), which were mostly developmental regulators, and maintained H3K27me3 levels in Ezh1+/-Ezh2Δ/Δ HSPCs. Even upon the complete depletion of Ezh1 and Ezh2, H2AK119ub1 levels were largely retained, and only a minimal number of Ezh1 core targets were de-repressed. These results indicate that genes marked with high levels of H3K27me3 and H2AK119ub1 are the core targets of polycomb complexes in HSPCs as well as MDS stem cells.
DOI	10.1016/j.isci.2018.10.008
PMID	30396150