title: MTA1 regulates higher-order chromatin structure and histone H1-chromatin interaction in-vivo.
abstract: In the current study, for the first time, we found that metastasis-associated gene 1 (MTA1) was a higher-order chromatin structure organizer that decondenses the interphase chromatin and mitotic chromosomes. MTA1 interacts dynamically with nucleosomes during the cell cycle progression, prominently contributing to the mitotic chromatin/chromosome structure transitions at both prophase and telophase. We showed that the decondensation of interphase chromatin by MTA1 was independent of Mi-2 chromatin remodeling activity. H1 was reported to stabilize the compact higher-order chromatin structure through its interaction with DNA. Our data showed that MTA1 caused a reduced H1-chromatin interaction in-vivo. Moreover, the dynamic MTA1-chromatin interaction in the cell cycle contributed to the periodical H1-chromatin interaction, which in turn modulated chromatin/chromosome transitions. Although MTA1 drove a global decondensation of chromatin structure, it changed the expression of only a small proportion of genes. After MTA1 overexpression, the up-regulated genes were distributed in clusters along with down-regulated genes on chromosomes at parallel frequencies.
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute/Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100021, China; Medical Research Center, Beijing ChaoYang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute/Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Haijuan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Cancer Institute/Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, State Key Laboratory of Molecular Oncology, Beijing 100021, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Ma
authors.affiliation: Department of Abdominal Surgery, Cancer Institute/Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, State Key Laboratory of Molecular Oncology, Beijing 100021, China.
authors.forename: Dongkui
authors.initials: D
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute/Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Chang
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute/Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute/Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute/Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute/Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute/Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100021, China. Electronic address: huang8849@126.com.
authors.forename: Changzhi
authors.initials: C
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute/Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100021, China. Electronic address: qianhaili001@163.com.
authors.forename: Haili
authors.initials: H
authors.lastname: Qian
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute/Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100021, China. Electronic address: qiminzhan@163.com.
authors.forename: Qimin
authors.initials: Q
authors.lastname: Zhan
mesh_terms: D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D015536:Down-Regulation / Q000502:physiology; D057809:HEK293 Cells; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators; D015854:Up-Regulation / Q000502:physiology
chemical_list: D006657:Histones; C089320:MTA1 protein, human; D009707:Nucleosomes; D012097:Repressor Proteins; D015534:Trans-Activators; D006655:Histone Deacetylases
keywords: Chromatin; Histone H1; MTA1; Nucleosome remodeling and histone deacetylation complex (NuRD); in-vivo