Epigeneitc silencing of ribosomal RNA genes by Mybbp1a

Journal of Biomedical Science

Research

Benjamin Yat-Ming Yung¹  Chang-Zheng Zhong²  Bertrand Chin-Ming Tan²  Chang-Ching Yang²  Chia-Ling Hsieh²  Yin-Hsiang Chou²  Hsuan Liu³ 

[1] Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong;Graduate Institute of Biomedical Sciences and Department of Biomedical Sciences, College of Medicine, Chang Gung University, 333, Kwei-San, Tao-Yuan, Taiwan;Molecular Medicine Research Center, Chang Gung University, 333, Kwei-San, Tao-Yuan, Taiwan;

关键词: HeLa Cell;    Ribosome Biogenesis;    rDNA Repeat;    rDNA Cluster;    rDNA Transcription;   

DOI  :  10.1186/1423-0127-19-57

 received in 2011-12-09, accepted in 2012-06-11,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundTranscription of the ribosomal RNA gene repeats by Pol I occurs in the nucleolus and is a fundamental step in ribosome biogenesis and protein translation. Due to tight coordination between ribosome biogenesis and cell proliferation, transcription of rRNA and stable maintenance of rDNA clusters are thought to be under intricate control by intercalated mechanisms, particularly at the epigenetic level.Methods and ResultsHere we identify the nucleolar protein Myb-binding protein 1a (Mybbp1a) as a novel negative regulator of rRNA expression. Suppression of rDNA transcription by Mybbp1a was linked to promoter regulation as illustrated by its binding to the chromatin around the hypermethylated, inactive rDNA gene promoters. Our data further showed that downregulation of Mybbp1a abrogated the local DNA methylation levels and histone marks associated with gene silencing, and altered the promoter occupancy of various factors such UBF and HDACs, consequently leading to elevated rRNA expression. Mechanistically, we propose that Mybbp1a maintains rDNA repeats in a silenced state while in association with the negative epigenetic modifiers HDAC1/2.ConclusionsResults from our present work reveal a previously unrecognized co-repressor role of Mybbp1a in rRNA expression. They are further consistent with the scenario that Mybbp1a is an integral constituent of the rDNA epigenetic regulation that underlies the balanced state of rDNA clusters.

【 授权许可】

Unknown   
© Tan et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.