Epigeneitc silencing of ribosomal RNA genes by Mybbp1a

Bertrand Chin Ming Tan, Chang Ching Yang, Chia Ling Hsieh, Yin Hsiang Chou, Chang Zheng Zhong, Benjamin Yat Ming Yung, Hsuan Liu

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Article number57
JournalJournal of Biomedical Science
Volume19
Issue number1
DOIs
Publication statusPublished - 2012
Externally publishedYes

Fingerprint

Ribosomal RNA
Ribosomal DNA
rRNA Genes
Carrier Proteins
Genes
Transcription
Epigenomics
Ribosomes
Histone Code
Co-Repressor Proteins
Cell proliferation
Protein Biosynthesis
Gene Silencing
DNA Methylation
Nuclear Proteins
Protein Binding
Histones
Chromatin
Down-Regulation
Maintenance

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Pharmacology (medical)

Cite this

Tan, B. C. M., Yang, C. C., Hsieh, C. L., Chou, Y. H., Zhong, C. Z., Yung, B. Y. M., & Liu, H. (2012). Epigeneitc silencing of ribosomal RNA genes by Mybbp1a. Journal of Biomedical Science, 19(1), [57]. https://doi.org/10.1186/1423-0127-19-57

Epigeneitc silencing of ribosomal RNA genes by Mybbp1a. / Tan, Bertrand Chin Ming; Yang, Chang Ching; Hsieh, Chia Ling; Chou, Yin Hsiang; Zhong, Chang Zheng; Yung, Benjamin Yat Ming; Liu, Hsuan.

In: Journal of Biomedical Science, Vol. 19, No. 1, 57, 2012.

Research output: Contribution to journalArticle

Tan, BCM, Yang, CC, Hsieh, CL, Chou, YH, Zhong, CZ, Yung, BYM & Liu, H 2012, 'Epigeneitc silencing of ribosomal RNA genes by Mybbp1a', Journal of Biomedical Science, vol. 19, no. 1, 57. https://doi.org/10.1186/1423-0127-19-57
Tan, Bertrand Chin Ming ; Yang, Chang Ching ; Hsieh, Chia Ling ; Chou, Yin Hsiang ; Zhong, Chang Zheng ; Yung, Benjamin Yat Ming ; Liu, Hsuan. / Epigeneitc silencing of ribosomal RNA genes by Mybbp1a. In: Journal of Biomedical Science. 2012 ; Vol. 19, No. 1.
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