Transcription inhibition suppresses nuclear blebbing and rupture independently of nuclear rigidity

Isabel K. Berg, Marilena L. Currey, Sarthak Gupta, Yasmin Berrada, Bao V. Nguyen, Mai Pho, Alison E. Patteson, J. M. Schwarz, Edward J. Banigan, Andrew D. Stephens

Research output: Contribution to journalArticlepeer-review

Abstract

Chromatin plays an essential role in the nuclear mechanical response and determining nuclear shape, which maintain nuclear compartmentalization and function. However, major genomic functions, such as transcription activity, might also impact cell nuclear shape via blebbing and rupture through their effects on chromatin structure and dynamics. To test this idea, we inhibited transcription with several RNA polymerase II inhibitors in wild-type cells and perturbed cells that presented increased nuclear blebbing. Transcription inhibition suppressed nuclear blebbing for several cell types, nuclear perturbations and transcription inhibitors. Furthermore, transcription inhibition suppressed nuclear bleb formation, bleb stabilization and bleb-based nuclear ruptures. Interestingly, transcription inhibition did not alter the histone H3 lysine 9 (H3K9) modification state, nuclear rigidity, and actin compression and contraction, which typically control nuclear blebbing. Polymer simulations suggested that RNA polymerase II motor activity within chromatin could drive chromatin motions that deform the nuclear periphery. Our data provide evidence that transcription inhibition suppresses nuclear blebbing and rupture, in a manner separate and distinct from chromatin rigidity.

Original languageEnglish (US)
Article numberjcs261547
JournalJournal of cell science
Volume136
Issue number20
DOIs
StatePublished - Oct 2023

Keywords

  • Chromatin
  • Mechanobiology
  • Nuclear blebbing
  • Nucleus

ASJC Scopus subject areas

  • Cell Biology

Fingerprint

Dive into the research topics of 'Transcription inhibition suppresses nuclear blebbing and rupture independently of nuclear rigidity'. Together they form a unique fingerprint.

Cite this