title: Epigenetic silencing of core histone genes by HERS in Drosophila.
abstract: Cell cycle-dependent expression of canonical histone proteins enables newly synthesized DNA to be integrated into chromatin in replicating cells. However, the molecular basis of cell cycle-dependency in the switching of histone gene regulation remains to be uncovered. Here, we report the identification and biochemical characterization of a molecular switcher, HERS (histone gene-specific epigenetic repressor in late S phase), for nucleosomal core histone gene inactivation in Drosophila. HERS protein is phosphorylated by a cyclin-dependent kinase (Cdk) at the end of S-phase. Phosphorylated HERS binds to histone gene regulatory regions and anchors HP1 and Su(var)3-9 to induce chromatin inactivation through histone H3 lysine 9 methylation. These findings illustrate a salient molecular switch linking epigenetic gene silencing to cell cycle-dependent histone production.
authors.affiliation: Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Saya
authors.initials: S
authors.lastname: Ito
authors.forename: Sally
authors.initials: S
authors.lastname: Fujiyama-Nakamura
authors.forename: Shuhei
authors.initials: S
authors.lastname: Kimura
authors.forename: Jinseon
authors.initials: J
authors.lastname: Lim
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kamoshida
authors.forename: Yumi
authors.initials: Y
authors.lastname: Shiozaki-Sato
authors.forename: Shun
authors.initials: S
authors.lastname: Sawatsubashi
authors.forename: Eriko
authors.initials: E
authors.lastname: Suzuki
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tanabe
authors.forename: Takashi
authors.initials: T
authors.lastname: Ueda
authors.forename: Takuya
authors.initials: T
authors.lastname: Murata
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kato
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Ohtake
authors.forename: Ryoji
authors.initials: R
authors.lastname: Fujiki
authors.forename: Tsuneharu
authors.initials: T
authors.lastname: Miki
authors.forename: Alexander
authors.initials: A
authors.lastname: Kouzmenko
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Takeyama
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Kato
mesh_terms: D000818:Animals; D002453:Cell Cycle; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006657:Histones / Q000235:genetics*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016196:S Phase
chemical_list: D029721:Drosophila Proteins; C571737:HERS protein, Drosophila; D006657:Histones; D012097:Repressor Proteins