2. Academic Validation
  3. Glutarylation of Histone H4 Lysine 91 Regulates Chromatin Dynamics

Glutarylation of Histone H4 Lysine 91 Regulates Chromatin Dynamics

  • Mol Cell. 2019 Nov 21;76(4):660-675.e9. doi: 10.1016/j.molcel.2019.08.018.
Xiucong Bao 1,  Zheng Liu 1,  Wei Zhang 2,  Kornelia Gladysz 3,  Yi Man Eva Fung 4,  Gaofei Tian 1,  Ying Xiong 1,  Jason Wing Hon Wong 5,  Karen Wing Yee Yuen 6,  Xiang David Li 7
Affiliations

Affiliations

  • 1 Department of Chemistry, University of Hong Kong, Pokfulam Road, Hong Kong, China.
  • 2 School of Biological Sciences, University of Hong Kong, Pokfulam Road, Hong Kong, China.
  • 3 School of Biomedical Sciences, University of Hong Kong, Pokfulam Road, Hong Kong, China.
  • 4 Department of Chemistry, University of Hong Kong, Pokfulam Road, Hong Kong, China; The State Key Laboratory on Synthetic Chemistry, University of Hong Kong, Pokfulam Road, Hong Kong, China.
  • 5 School of Biomedical Sciences, University of Hong Kong, Pokfulam Road, Hong Kong, China. Electronic address: jwhwong@hku.hk.
  • 6 School of Biological Sciences, University of Hong Kong, Pokfulam Road, Hong Kong, China. Electronic address: kwyyuen@hku.hk.
  • 7 Department of Chemistry, University of Hong Kong, Pokfulam Road, Hong Kong, China. Electronic address: xiangli@hku.hk.
PMID: 31542297 DOI: 10.1016/j.molcel.2019.08.018
Abstract

Histone posttranslational modifications (PTMs) regulate chromatin structure and dynamics during various DNA-associated processes. Here, we report that lysine glutarylation (Kglu) occurs at 27 lysine residues on human core histones. Using semi-synthetic glutarylated histones, we show that an evolutionarily conserved Kglu at histone H4K91 destabilizes nucleosome in vitro. In Saccharomyces cerevisiae, the replacement of H4K91 by glutamate that mimics Kglu influences chromatin structure and thereby results in a global upregulation of transcription and defects in cell-cycle progression, DNA damage repair, and telomere silencing. In mammalian cells, H4K91glu is mainly enriched at promoter regions of highly expressed genes. A downregulation of H4K91glu is tightly associated with chromatin condensation during mitosis and in response to DNA damage. The cellular dynamics of H4K91glu is controlled by SIRT7 as a deglutarylase and KAT2A as a glutaryltransferase. This study designates a new histone MARK (Kglu) as a new regulatory mechanism for chromatin dynamics.

Keywords

DNA damage; KAT2A; Sirt7; chemical reporter; chromatin condensation; epigenetics; histone lysine glutarylation; nucleosome dynamics; α-KADH.

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