据介绍，组织稳态需要在压力下维持功能完整性。压力的主要来源是机械力，其作用于细胞、细胞核和染色质，但如何保护基因组免受机械压力尚不清楚。

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

Author: Michele M. Nava, Yekaterina A. Miroshnikova, Leah C. Biggs, Daniel B. Whitefield, Franziska Metge, Jorge Boucas, Helena Vihinen, Eija Jokitalo, Xinping Li, Juan Manuel García Arcos, Bernd Hoffmann, Rudolf Merkel, Carien M. Niessen, Kris Noel Dahl, Sara A. Wickstrm

Issue&Volume: 2020-04-16

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.

DOI: 10.1016/j.cell.2020.03.052

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30345-7