Transcription upregulation via force-induced direct stretching of chromatin

Arash Tajik, Yuejin Zhang, Fuxiang Wei, Jian Sun, Qiong Jia, Wenwen Zhou, Rishi Singh, Nimish Khanna, Andrew S. Belmont, Ning Wang

Research output: Contribution to journalArticlepeer-review

Abstract

Mechanical forces play critical roles in the function of living cells. However, the underlying mechanisms of how forces influence nuclear events remain elusive. Here, we show that chromatin deformation as well as force-induced transcription of a green fluorescent protein (GFP)-tagged bacterial-chromosome dihydrofolate reductase (DHFR) transgene can be visualized in a living cell by using three-dimensional magnetic twisting cytometry to apply local stresses on the cell surface via an Arg-Gly-Asp-coated magnetic bead. Chromatin stretching depended on loading direction. DHFR transcription upregulation was sensitive to load direction and proportional to the magnitude of chromatin stretching. Disrupting filamentous actin or inhibiting actomyosin contraction abrogated or attenuated force-induced DHFR transcription, whereas activating endogenous contraction upregulated force-induced DHFR transcription. Our findings suggest that local stresses applied to integrins propagate from the tensed actin cytoskeleton to the LINC complex and then through lamina-chromatin interactions to directly stretch chromatin and upregulate transcription.

Original languageEnglish (US)
Pages (from-to)1287-1296
Number of pages10
JournalNature Materials
Volume15
Issue number12
DOIs
StatePublished - Dec 1 2016

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanics of Materials
  • Mechanical Engineering

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