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Heterochromatin-Driven Nuclear Softening Protects the Genome against Mechanical Stress-Induced Damage.

Abstract：

: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.

journal_name

Cell

journal_title

Cell

authors

Nava MM,Miroshnikova YA,Biggs LC,Whitefield DB,Metge F,Boucas J,Vihinen H,Jokitalo E,Li X,García Arcos JM,Hoffmann B,Merkel R,Niessen CM,Dahl KN,Wickström SA

doi

10.1016/j.cell.2020.03.052

subject

Has Abstract

pub_date

2020-05-14 00:00:00

pages

800-817.e22

issue

4

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(20)30345-7

journal_volume

181

pub_type

杂志文章

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