Epigenetic Silencing of Core Histone Genes by HERS in Drosophila

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 identificat...

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Bibliographic Details
Published in:Molecular cell 2012-02, Vol.45 (4), p.494-504
Main Authors: Ito, Saya, Fujiyama-Nakamura, Sally, Kimura, Shuhei, Lim, Jinseon, Kamoshida, Yuki, Shiozaki-Sato, Yumi, Sawatsubashi, Shun, Suzuki, Eriko, Tanabe, Masahiko, Ueda, Takashi, Murata, Takuya, Kato, Hiromi, Ohtake, Fumiaki, Fujiki, Ryoji, Miki, Tsuneharu, Kouzmenko, Alexander, Takeyama, Ken-ichi, Kato, Shigeaki
Format: Article
Language:English
Subjects:
Animals
Cell Cycle
Chromatin
Cyclin-dependent kinase
DNA
DNA methylation
Drosophila
Drosophila - genetics
Drosophila Proteins - genetics
Drosophila Proteins - metabolism
Drosophila Proteins - physiology
Epigenesis, Genetic
epigenetics
Gene Expression Regulation
Gene regulation
Gene Silencing
HER protein
Histone H3
Histones
Histones - genetics
interphase
Lysine
methylation
Phosphorylation
Promoter Regions, Genetic
regulator genes
Regulatory sequences
Repressor Proteins - genetics
Repressor Proteins - metabolism
Repressor Proteins - physiology
Repressors
S Phase
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Summary: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. ► The late S phase repressor of fly histone gene, HERS, was genetically identified ► Cdk phosphorylates HERS in the late S-phase ► HERS induces chromatin silencing at histone gene loci by HP1/Su(var)3-9 recruitment
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2011.12.029