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Glutarylation of Histone H4 Lysine 91 Regulates Chromatin Dynamics

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 evolutio...

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Bibliographic Details
Published in:Molecular cell 2019-11, Vol.76 (4), p.660-675.e9
Main Authors: Bao, Xiucong, Liu, Zheng, Zhang, Wei, Gladysz, Kornelia, Fung, Yi Man Eva, Tian, Gaofei, Xiong, Ying, Wong, Jason Wing Hon, Yuen, Karen Wing Yee, Li, Xiang David
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Language:English
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Summary: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. [Display omitted] •H4K91glu is a new histone mark enriched at promoters of highly expressed genes•H4K91glu destabilizes nucleosome by affecting (H2A/H2B) and (H3/H4)2 interaction•H4K91glu is regulated by KAT2A and Sirt7 as its “writer” and “eraser,” respectively•H4K91glu regulates chromatin structure and dynamics in response to DNA damage Bao et al. identify H4 Lys91 glutarylation (H4K91glu) as a new histone mark for active gene expression. H4K91glu is “written” and “erased” by KAT2A and Sirt7, respectively. Sirt7-catalyzed removal of H4K91glu is associated with chromatin condensation during mitosis and in response to DNA damage.
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2019.08.018