title: Chromodomain protein CDYL is required for transmission/restoration of repressive histone marks.
abstract: Faithful transmission or restoration of epigenetic information such as repressive histone modifications through generations is critical for the maintenance of cell identity. We report here that chromodomain Y-like protein (CDYL), a chromodomain-containing transcription corepressor, is physically associated with chromatin assembly factor 1 (CAF-1) and the replicative helicase MCM complex. We showed that CDYL bridges CAF-1 and MCM, facilitating histone transfer and deposition during DNA replication. We demonstrated that CDYL recruits histone-modifying enzymes G9a, SETDB1, and EZH2 to replication forks, leading to the addition of H3K9me2/3 and H3K27me2/3 on newly deposited histone H3. Significantly, depletion of CDYL impedes early S phase progression and sensitizes cells to DNA damage. Our data indicate that CDYL plays an important role in the transmission/restoration of repressive histone marks, thereby preserving the epigenetic landscape for the maintenance of cell identity.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Shumeng
authors.initials: S
authors.lastname: Liu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Huajing
authors.initials: H
authors.lastname: Yu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Xiaohan
authors.initials: X
authors.lastname: Yang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Guojia
authors.initials: G
authors.lastname: Xie
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Wanjin
authors.initials: W
authors.lastname: Li
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Bosen
authors.initials: B
authors.lastname: Xu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Luyang
authors.initials: L
authors.lastname: Sun
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.|Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.|Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Shang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liang
mesh_terms: D002843:Chromatin / Q000378:metabolism; D056970:Co-Repressor Proteins; D004249:DNA Damage; D004261:DNA Replication; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000378:metabolism; D044127:Epigenesis, Genetic; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006836:Hydro-Lyases; D008239:Lysine / Q000378:metabolism; D064110:Minichromosome Maintenance Proteins / Q000378:metabolism; D011496:Protein Methyltransferases / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D016196:S Phase / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C489780:CNOT8 protein, human; D002843:Chromatin; D056970:Co-Repressor Proteins; D006657:Histones; D011506:Proteins; D014157:Transcription Factors; D011496:Protein Methyltransferases; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D011495:Histone-Lysine N-Methyltransferase; C454062:SETDB1 protein, human; D064110:Minichromosome Maintenance Proteins; C118458:CDYL protein, human; D006836:Hydro-Lyases; D008239:Lysine
keywords: CAF-1; CDYL; MCM; epigenetic inheritance; histone modification