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http://hdl.handle.net/10397/6555
| Title: | Epigeneitc silencing of ribosomal RNA genes by Mybbp1a | Authors: | Tan, BCM Yang, CC Hsieh, CL Chou, YH Zhong, CZ Yung, BYM Liu, H |
Issue Date: | 2012 | Source: | Journal of biomedical science, 2012, v. 19, no. 1, 57, p.1- | Abstract: | Background: Transcription 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 Results: Here 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. Conclusions: Results 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. |
Publisher: | BioMed Central Ltd. | Journal: | Journal of biomedical science | ISSN: | 1021-7770 (print) 1423-0127 (online) |
DOI: | 10.1186/1423-0127-19-57 | Rights: | © 2012 Tan et al.; licensee 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. |
| Appears in Collections: | Journal/Magazine Article |
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| Tan_Epigeneitc_RNA_Mybbp1a.pdf | 1.09 MB | Adobe PDF | View/Open |
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