title: Disruption of human vigilin impairs chromosome condensation and segregation.
abstract: Appropriate packaging and condensation are critical for eukaryotic chromatin's accommodation and separation during cell division. Human vigilin, a multi-KH-domain nucleic acid-binding protein, is associated with alpha satellites of centromeres. DDP1, a vigilin's homolog, is implicated with chromatin condensation and segregation. The expression of vigilin was previously reported to elevate in highly proliferating tissues and increased in a subset of hepatocellular carcinoma patients. Other studies showed that vigilin interacts with CTCF, contributes to regulation of imprinted genes Igf2/H19, and colocalizes with HP1α on heterochromatic satellite 2 and β-satellite repeats. These studies indicate that human vigilin might be involved in chromatin remodeling and regular cell growth. To investigate the potential role of human vigilin in cell cycle, the correlations between vigilin and chromosomal condensation and segregation were studied. Depletion of human vigilin by RNA interference in HepG2 cells resulted in chromosome undercondensation and various chromosomal defects during mitotic phase, including chromosome misalignments, lagging chromosomes, and chromosome bridges. Aberrant polyploid nucleus in telophase was also observed. Unlike the abnormal staining pattern of chromosomes, the shape of spindle was normal. Furthermore, the chromatin showed a greater sensitivity to MNase digestion. Collectively, our findings show that human vigilin apparently participates in chromatin condensation and segregation.
authors.affiliation: Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wei
authors.affiliation: Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Junhong
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Shen
authors.affiliation: Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Shuwang
authors.initials: S
authors.lastname: Duan
authors.affiliation: Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Rongce
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Qiuying
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, 610041, Sichuan, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, 610041, Sichuan, China.|Sichuan University "985 Project-Science and Technology Innovation Platform for Novel Drug Development", Chengdu, 610041, Sichuan, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Qin
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D002503:Centromere / Q000378:metabolism; D002843:Chromatin / Q000187:drug effects* / Q000378:metabolism; D000090266:Chromobox Protein Homolog 5; D020090:Chromosome Segregation / Q000502:physiology*; D002877:Chromosomes, Human / Q000235:genetics / Q000502:physiology*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism; D008938:Mitosis / Q000502:physiology; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: C000715594:CBX5 protein, human; D002843:Chromatin; D016601:RNA-Binding Proteins; D000090266:Chromobox Protein Homolog 5; C075197:high density lipoprotein binding protein
keywords: chromatin compaction; chromosomal architecture; mitotic defects; vigilin