Epigenetic repression of ribosomal RNA transcription by ROCK-dependent aberrant cytoskeletal organization.

Abstract:

:It is known that ribosomal RNA (rRNA) synthesis is regulated by cellular energy and proliferation status. In this study, we investigated rRNA gene transcription in response to cytoskeletal stress. Our data revealed that the cell shape constrained by isotropic but not elongated micropatterns in HeLa cells led to a significant reduction in rRNA transcription dependent on ROCK. Expression of a dominant-active form of ROCK also repressed rRNA transcription. Isotropic constraint and ROCK over-activation led to different types of aberrant F-actin organization, but their suppression effects on rRNA transcription were similarly reversed by inhibition of histone deacetylase (HDAC) or overexpression of a dominant negative form of Nesprin, which shields the signal transmitted from actin filament to the nuclear interior. We further showed that the binding of HDAC1 to the active fraction of rDNA genes is increased by ROCK over-activation, thus reducing H3K9/14 acetylation and suppressing transcription. Our results demonstrate an epigenetic control of active rDNA genes that represses rRNA transcription in response to the cytoskeletal stress.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Wu TH,Kuo YY,Lee HH,Kuo JC,Ou MH,Chang ZF

doi

10.1038/srep28685

subject

Has Abstract

pub_date

2016-06-28 00:00:00

pages

28685

issn

2045-2322

pii

srep28685

journal_volume

6

pub_type

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