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| Status |
Public on Sep 16, 2019 |
| Title |
Glutarylation of Histone H4 Lysine 91 Regulates Chromatin Dynamics |
| Organisms |
Saccharomyces cerevisiae; Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Chromatin is decorated with diverse histone posttranslational modifications (PTMs) that are involved in regulating chromatin structure and dynamics during various DNA-associated processes such as gene transcription, DNA replication and DNA damage repair. Here, we combine a chemical reporter with mass spectrometry to identify a new class of histone PTM, lysine glutarylation (Kglu), occurring at 27 lysine residues on human core histones. The characterization of an evolutionarily conserved Kglu mark at histone H4 lysine 91 (H4K91glu) using a semisynthetic glutarylated protein reveals that this negatively charged modification greatly destabilizes nucleosome by weakening the interactions between histone H2A/H2B dimers and H3/H4 tetramer in vitro. The replacement of H4K91 by glutamic acid in S. cerevisiae to mimic glutarylation influences chromatin structure and thereby results in a global up-regulation of transcription and defects in cell cycle progression, DNA damage repair and telomere silencing in vivo. In mammalian cells, H4K91glu is mainly enriched at promoter regions of highly expressed genes. A down-regulation 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.
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| Overall design |
ChIP-seq and RNA-seq
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| Web link |
https://www.sciencedirect.com/science/article/pii/S1097276519306574?via%3Dihub
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| |
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| Contributor(s) |
Li XD, Wong JW, Bao X |
| Citation(s) |
31542297 |
| Submission date |
May 28, 2019 |
| Last update date |
Dec 16, 2019 |
| Contact name |
Jason Wong |
| E-mail(s) |
jwhwong@hku.hk
|
| Phone |
+852 3917 9187
|
| Organization name |
The University of Hong Kong (HKU)
|
| Street address |
L1-51, Laboratory Block, 21 Sassoon Road
|
| City |
Hong Kong |
| State/province |
42-100 |
| ZIP/Postal code |
00000 |
| Country |
Hong Kong |
| |
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| Platforms (2) |
| GPL23227 |
BGISEQ-500 (Homo sapiens) |
| GPL25927 |
BGISEQ-500 (Saccharomyces cerevisiae) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA545040 |
| SRA |
SRP199609 |
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