title: CDK2-dependent phosphorylation of Suv39H1 is involved in control of heterochromatin replication during cell cycle progression.
abstract: Although several studies have suggested that the functions of heterochromatin regulators may be regulated by post-translational modifications during cell cycle progression, regulation of the histone methyltransferase Suv39H1 is not fully understood. Here, we demonstrate a direct link between Suv39H1 phosphorylation and cell cycle progression. We show that CDK2 phosphorylates Suv39H1 at Ser391 and these phosphorylation levels oscillate during the cell cycle, peaking at S phase and maintained during S-G2-M phase. The CDK2-mediated phosphorylation of Suv39H1 at Ser391 results in preferential dissociation from chromatin. Furthermore, phosphorylation-mediated dissociation of Suv39H1 from chromatin causes an enhanced occupancy of JMJD2A histone demethylase on heterochromatin and alterations in inactive histone marks. Overexpression of phospho-mimic Suv39H1 induces early replication of heterochromatin, suggesting the importance of Suv39H1 phosphorylation in the replication of heterochromatin. Moreover, overexpression of phospho-defective Suv39H1 caused altered replication timing of heterochromatin and increases sensitivity to replication stress. Collectively, our data suggest that phosphorylation-mediated modulation of Suv39H1-chromatin association may be an initial step in heterochromatin replication.
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea Initiative for Biological Function & Systems, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Su Hyung
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea Initiative for Biological Function & Systems, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Seung Eun
authors.initials: SE
authors.lastname: Yu
authors.affiliation: Division of Molecular and Life Science, Hanyang University, Ansan, Republic of Korea.
authors.forename: Young Gyu
authors.initials: YG
authors.lastname: Chai
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea Initiative for Biological Function & Systems, Yonsei University, Seoul 120-749, Republic of Korea ykjang@yonsei.ac.kr.
authors.forename: Yeun Kyu
authors.initials: YK
authors.lastname: Jang
mesh_terms: D002453:Cell Cycle / Q000235:genetics*; D002460:Cell Line; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism*; D006570:Heterochromatin / Q000378:metabolism*; D056466:Histone Demethylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008745:Methylation; D008780:Methyltransferases / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D012694:Serine / Q000378:metabolism
chemical_list: D006570:Heterochromatin; D006657:Histones; D012097:Repressor Proteins; D012694:Serine; D056466:Histone Demethylases; C407843:SUV39H1 protein, human; D008780:Methyltransferases; D051357:Cyclin-Dependent Kinase 2
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