title: The spatiotemporal dynamics of chromatin protein HP1α is essential for accurate chromosome segregation during cell division.
abstract: Heterochromatin protein 1α (HP1α) is involved in regulation of chromatin plasticity, DNA damage repair, and centromere dynamics. HP1α detects histone dimethylation and trimethylation of Lys-9 via its chromodomain. HP1α localizes to heterochromatin in interphase cells but is liberated from chromosomal arms at the onset of mitosis. However, the structural determinants required for HP1α localization in interphase and the regulation of HP1α dynamics have remained elusive. Here we show that centromeric localization of HP1α depends on histone H3 Lys-9 trimethyltransferase SUV39H1 activity in interphase but not in mitotic cells. Surprisingly, HP1α liberates from chromosome arms in early mitosis. To test the role of this dissociation, we engineered an HP1α construct that persistently localizes to chromosome arms. Interestingly, persistent localization of HP1α to chromosome arms perturbs accurate kinetochore-microtubule attachment due to an aberrant distribution of chromosome passenger complex and Sgo1 from centromeres to chromosome arms that prevents resolution of sister chromatids. Further analyses showed that Mis14 and perhaps other PXVXL-containing proteins are involved in directing localization of HP1α to the centromere in mitosis. Taken together, our data suggest a model in which spatiotemporal dynamics of HP1α localization to centromere is governed by two distinct structural determinants. These findings reveal a previously unrecognized but essential link between HP1α-interacting molecular dynamics and chromosome plasticity in promoting accurate cell division.
authors.affiliation: Anhui Key Laboratory for Cellular Dynamics and Chemical Biology and Hefei National Laboratory for Physical Sciences at the Microscale, Hefei 230026, China.
authors.forename: Lingluo
authors.initials: L
authors.lastname: Chu
authors.affiliation: Anhui Key Laboratory for Cellular Dynamics and Chemical Biology and Hefei National Laboratory for Physical Sciences at the Microscale, Hefei 230026, China.
authors.forename: Yuda
authors.initials: Y
authors.lastname: Huo
authors.affiliation: Anhui Key Laboratory for Cellular Dynamics and Chemical Biology and Hefei National Laboratory for Physical Sciences at the Microscale, Hefei 230026, China,; Departments of Physiology and Morehouse School of Medicine, Atlanta, Georgia 30310.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Departments of Physiology and Morehouse School of Medicine, Atlanta, Georgia 30310; Department of Cellular Biology, University of Georgia, Athens, Georgia 30602.
authors.forename: Phil
authors.initials: P
authors.lastname: Yao
authors.affiliation: Departments of Neurobiology, Morehouse School of Medicine, Atlanta, Georgia 30310.
authors.forename: Kelwyn
authors.initials: K
authors.lastname: Thomas
authors.affiliation: Anhui Key Laboratory for Cellular Dynamics and Chemical Biology and Hefei National Laboratory for Physical Sciences at the Microscale, Hefei 230026, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Anhui Key Laboratory for Cellular Dynamics and Chemical Biology and Hefei National Laboratory for Physical Sciences at the Microscale, Hefei 230026, China,; Departments of Physiology and Morehouse School of Medicine, Atlanta, Georgia 30310.
authors.forename: Tongge
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Guangzhou Women and Children's Medical Center, Guangzhou 510623, China, and.
authors.forename: Guanglan
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Departments of Physiology and Morehouse School of Medicine, Atlanta, Georgia 30310.
authors.forename: Maryam
authors.initials: M
authors.lastname: Chaudhry
authors.affiliation: Anhui Key Laboratory for Cellular Dynamics and Chemical Biology and Hefei National Laboratory for Physical Sciences at the Microscale, Hefei 230026, China,; Departments of Physiology and Morehouse School of Medicine, Atlanta, Georgia 30310.
authors.forename: Gregory
authors.initials: G
authors.lastname: Adams
authors.affiliation: Departments of Physiology and Morehouse School of Medicine, Atlanta, Georgia 30310.
authors.forename: Winston
authors.initials: W
authors.lastname: Thompson
authors.affiliation: Anhui Key Laboratory for Cellular Dynamics and Chemical Biology and Hefei National Laboratory for Physical Sciences at the Microscale, Hefei 230026, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Dou
authors.affiliation: Anhui Key Laboratory for Cellular Dynamics and Chemical Biology and Hefei National Laboratory for Physical Sciences at the Microscale, Hefei 230026, China.
authors.forename: Changjiang
authors.initials: C
authors.lastname: Jin
authors.affiliation: Guangzhou Women and Children's Medical Center, Guangzhou 510623, China, and. Electronic address: heping-20088@163.com.
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.affiliation: Anhui Key Laboratory for Cellular Dynamics and Chemical Biology and Hefei National Laboratory for Physical Sciences at the Microscale, Hefei 230026, China,; Departments of Physiology and Morehouse School of Medicine, Atlanta, Georgia 30310. Electronic address: yaoxb@ustc.edu.cn.
authors.forename: Xuebiao
authors.initials: X
authors.lastname: Yao
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D002503:Centromere / Q000378:metabolism; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D020090:Chromosome Segregation; D002877:Chromosomes, Human / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006570:Heterochromatin / Q000378:metabolism; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D008780:Methyltransferases / Q000378:metabolism; D008938:Mitosis; D021381:Protein Transport; D012097:Repressor Proteins / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism
chemical_list: C000715594:CBX5 protein, human; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin; D012097:Repressor Proteins; C496644:SGO1 protein, human; D000090266:Chromobox Protein Homolog 5; C407843:SUV39H1 protein, human; D008780:Methyltransferases
keywords: Cell Cycle; Cell Division; Centromere; Checkpoint Control; Chromatin; Chromatin Modification; Chromatin Remodeling; Chromatin Structure; Chromosomes; Cytokinesis
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