Journal
NUCLEIC ACIDS RESEARCH
Volume 48, Issue 17, Pages 9538-9549Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkaa663
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Funding
- National Natural Science Foundation of China [91753130, 21572191]
- Hong Kong Research Grants Council Collaborative Research Fund [CRF C7029-15G, CRF C7028-19GF]
- Areas of Excellence Scheme [AoE/P-705/16]
- General Research Fund [GRF 17121120, 17126618, 17125917]
- Areas of Excellence Scheme, General Research Fund
- Hong Kong Research Grants Council Collaborative Research Fund
- National Natural Science Foundation of China
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Posttranslational modifications (PTMs) of histones represent a crucial regulatory mechanism of nucleosome and chromatin dynamics in various of DNA-based cellular processes, such as replication, transcription and DNA damage repair. Lysine succinylation (Ksucc) is a newly identified histone PTM, but its regulation and function in chromatin remain poorly understood. Here, we utilized an expressed protein ligation (EPL) strategy to synthesize histone H4 with site-specific succinylation at K77 residue (H4K77succ), an evolutionarily conserved succinylation site at the nucleosomal DNA-histone interface. We then assembled mononucleosomes with the semisynthetic H4K77succ in vitro. We demonstrated that this succinylation impacts nucleosome dynamics and promotes DNA unwrapping from the histone surface, which allows proteins such as transcription factors to rapidly access buried regions of the nucleosomal DNA. In budding yeast, a lysine-to-glutamic acid mutation, which mimics Ksucc, at the H4K77 site reduced nucleosome stability and led to defects in DNA damage repair and telomere silencing in vivo. Our findings revealed this uncharacterized histone modification has important roles in nucleosome and chromatin dynamics.
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