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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2016

Erschienen:

2016

Enthalten in:

Zur Gesamtaufnahme - volume:6

Enthalten in:

Scientific reports - 6(2016) vom: 28. Juni, Seite 28685

Sprache:

Englisch

Beteiligte Personen:

Wu, Tse-Hsiang [VerfasserIn]
Kuo, Yuan-Yeh [VerfasserIn]
Lee, Hsiao-Hui [VerfasserIn]
Kuo, Jean-Cheng [VerfasserIn]
Ou, Meng-Hsin [VerfasserIn]
Chang, Zee-Fen [VerfasserIn]

Links:

Volltext

Themen:

DNA, Ribosomal
EC 2.7.11.1
EC 3.5.1.98
HDAC1 protein, human
Histone Deacetylase 1
Journal Article
RNA, Ribosomal
Research Support, Non-U.S. Gov't
Rho-Associated Kinases

Anmerkungen:

Date Completed 10.05.2018

Date Revised 13.11.2018

published: Electronic

Citation Status MEDLINE

doi:

10.1038/srep28685

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM261816608