生物
异染色质
机械转化
DNA损伤
细胞核
细胞生物学
遗传学
核心
DNA
染色质
作者
Michele M. Nava,Yekaterina A. Miroshnikova,Leah C. Biggs,Daniel B. Whitefield,Franziska Metge,Jorge Bouças,Helena Vihinen,Eija Jokitalo,Xinping Li,Juan Manuel GARCIA ARCOS,Bernd Hoffmann,Rudolf Merkel,Carien M. Niessen,Kris Noel Dahl,Sara A. Wickström
出处
期刊:Cell
[Elsevier]
日期:2020-05-01
卷期号:181 (4): 800-817.e22
被引量:396
标识
DOI:10.1016/j.cell.2020.03.052
摘要
Summary
Tissue homeostasis requires maintenance of functional integrity under stress. A central source of stress is mechanical force that acts on cells, their nuclei, and chromatin, but how the genome is protected against mechanical stress is unclear. We show that mechanical stretch deforms the nucleus, which cells initially counteract via a calcium-dependent nuclear softening driven by loss of H3K9me3-marked heterochromatin. The resulting changes in chromatin rheology and architecture are required to insulate genetic material from mechanical force. Failure to mount this nuclear mechanoresponse results in DNA damage. Persistent, high-amplitude stretch induces supracellular alignment of tissue to redistribute mechanical energy before it reaches the nucleus. This tissue-scale mechanoadaptation functions through a separate pathway mediated by cell-cell contacts and allows cells/tissues to switch off nuclear mechanotransduction to restore initial chromatin state. Our work identifies an unconventional role of chromatin in altering its own mechanical state to maintain genome integrity in response to deformation.
科研通智能强力驱动
Strongly Powered by AbleSci AI