title: 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.
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei, Taiwan 100, R.O.C.
authors.forename: Tse-Hsiang
authors.initials: TH
authors.lastname: Wu
authors.affiliation: Institute of Oncology, College of Medicine, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 100, Taiwan, R.O.C.
authors.forename: Yuan-Yeh
authors.initials: YY
authors.lastname: Kuo
authors.affiliation: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, No.155, Sec.2, Linong Street, Taipei, 112, Taiwan, R.O.C.
authors.forename: Hsiao-Hui
authors.initials: HH
authors.lastname: Lee
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, No.155, Sec.2, Linong Street, Taipei, 112, Taiwan, R.O.C.
authors.forename: Jean-Cheng
authors.initials: JC
authors.lastname: Kuo
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, No.155, Sec.2, Linong Street, Taipei, 112, Taiwan, R.O.C.
authors.forename: Meng-Hsin
authors.initials: MH
authors.lastname: Ou
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, No.155, Sec.2, Linong Street, Taipei, 112, Taiwan, R.O.C.
authors.forename: Zee-Fen
authors.initials: ZF
authors.lastname: Chang
mesh_terms: D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism*; D004275:DNA, Ribosomal / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000502:physiology*; D006367:HeLa Cells; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D012335:RNA, Ribosomal / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic / Q000502:physiology*; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D004275:DNA, Ribosomal; D012335:RNA, Ribosomal; D054460:rho-Associated Kinases; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1