Histone H1 deamidation facilitates chromatin relaxation for DNA repair

The formation of accessible chromatin around DNA double-strand breaks is essential for their efficient repair<sup>1</sup>. Although the linker histone H1 is known to facilitate higher-order chromatin compaction<sup>2,3</sup>, the mechanisms by which H1 modifications regulate chromatin relaxation in response to DNA damage are unclear. Here we show that CTP synthase 1 (CTPS1)-catalysed deamidation of H1 asparagine residues 76 and 77 triggers the sequential acetylation of lysine 75 following DNA damage, and this dual modification of H1 is associated with chromatin opening. Mechanistically, the histone acetyltransferase p300 showed a preference for deamidated H1 as a substrate, establishing H1 deamidation as a prerequisite for subsequent acetylation. Moreover, high expression of CTPS1 was associated with resistance to cancer radiotherapy, in both mouse xenograft models and clinical cohorts. These findings provide new insights into how linker histones regulate dynamic chromatin alterations in the DNA damage response.

Authors

Institutions

Publication Details

Journal
Nature
Published
2025-04-16
DOI
https://doi.org/10.1038/s41586-025-08835-0
Citations
20
Primary Topic
Biochemical and Molecular Research
Type
article
Field-Weighted Citation Impact
15.31
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Histone H1 deamidation facilitates chromatin relaxation for DNA repair

Chaohua Liu, Qian Zhu, Shunichi Takeda, Xiaopeng Lu et al.
20 citations
Nature
Biochemical and Molecular Research
15.31
article

Histone H1 deamidation facilitates chromatin relaxation for DNA repair

Chaohua Liu, Qian Zhu, Shunichi Takeda, Xiaopeng Lu, Tingting Feng, Qingren Meng, Wei‐Guo Zhu, Wenxin Zhan, Mengyan Li, Feng Chen, Jun Zhang, Yu Zhang, Ming Tang, Yuxin Shu, Yuan Tian, Wei-Han Tao
article en
20 citations

Abstract

The formation of accessible chromatin around DNA double-strand breaks is essential for their efficient repair<sup>1</sup>. Although the linker histone H1 is known to facilitate higher-order chromatin compaction<sup>2,3</sup>, the mechanisms by which H1 modifications regulate chromatin relaxation in response to DNA damage are unclear. Here we show that CTP synthase 1 (CTPS1)-catalysed deamidation of H1 asparagine residues 76 and 77 triggers the sequential acetylation of lysine 75 following DNA damage, and this dual modification of H1 is associated with chromatin opening. Mechanistically, the histone acetyltransferase p300 showed a preference for deamidated H1 as a substrate, establishing H1 deamidation as a prerequisite for subsequent acetylation. Moreover, high expression of CTPS1 was associated with resistance to cancer radiotherapy, in both mouse xenograft models and clinical cohorts. These findings provide new insights into how linker histones regulate dynamic chromatin alterations in the DNA damage response.

NatureVol. 641(8063)
Wannan Medical College (CN), Peking University (CN), Fudan University Shanghai Cancer Center (CN), Shenzhen University Health Science Center (CN), Shanghai First Maternity and Infant Hospital (CN)
Openalex Percentile: Top 1%
Biochemical and Molecular Research
15.31
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.