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Histone H3.3 phosphorylation promotes heterochromatin formation by inhibiting H3K9/K36 histone demethylase.
Udugama, Maheshi; Vinod, Benjamin; Chan, F Lyn; Hii, Linda; Garvie, Andrew; Collas, Philippe; Kalitsis, Paul; Steer, David; Das, Partha P; Tripathi, Pratibha; Mann, Jeffrey R; Voon, Hsiao P J; Wong, Lee H.
Affiliation
  • Udugama M; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
  • Vinod B; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
  • Chan FL; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
  • Hii L; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
  • Garvie A; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
  • Collas P; Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, 0317 Oslo, Norway.
  • Kalitsis P; Department of Immunology and Transfusion Medicine, Oslo University Hospital, 0424 Oslo, Norway.
  • Steer D; Victorian Clinical Genetics Service, Murdoch Children's Research Institute and Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Parkville, Victoria 3052, Australia.
  • Das PP; Biomedical Proteomics Facility, Monash University, Wellington Road, Clayton, Victoria 3800, Australia.
  • Tripathi P; Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
  • Mann JR; Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
  • Voon HPJ; Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
  • Wong LH; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
Nucleic Acids Res ; 50(8): 4500-4514, 2022 05 06.
Article in En | MEDLINE | ID: mdl-35451487
ABSTRACT
Histone H3.3 is an H3 variant which differs from the canonical H3.1/2 at four residues, including a serine residue at position 31 which is evolutionarily conserved. The H3.3 S31 residue is phosphorylated (H3.3 S31Ph) at heterochromatin regions including telomeres and pericentric repeats. However, the role of H3.3 S31Ph in these regions remains unknown. In this study, we find that H3.3 S31Ph regulates heterochromatin accessibility at telomeres during replication through regulation of H3K9/K36 histone demethylase KDM4B. In mouse embryonic stem (ES) cells, substitution of S31 with an alanine residue (H3.3 A31 -phosphorylation null mutant) results in increased KDM4B activity that removes H3K9me3 from telomeres. In contrast, substitution with a glutamic acid (H3.3 E31, mimics S31 phosphorylation) inhibits KDM4B, leading to increased H3K9me3 and DNA damage at telomeres. H3.3 E31 expression also increases damage at other heterochromatin regions including the pericentric heterochromatin and Y chromosome-specific satellite DNA repeats. We propose that H3.3 S31Ph regulation of KDM4B is required to control heterochromatin accessibility of repetitive DNA and preserve chromatin integrity.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Heterochromatin / Histones Limits: Animals Language: En Journal: Nucleic Acids Res Year: 2022 Type: Article Affiliation country: Australia
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Heterochromatin / Histones Limits: Animals Language: En Journal: Nucleic Acids Res Year: 2022 Type: Article Affiliation country: Australia