Epigeneitc silencing of ribosomal RNA genes by Mybbp1a.
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.


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.
Graduate Institute of Biomedical Sciences and Department of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan 333, Taiwan.
Bertrand Chin-Ming
BC
Tan
Chang-Ching
CC
Yang
Chia-Ling
CL
Hsieh
Yin-Hsiang
YH
Chou
Chang-Zheng
CZ
Zhong
Benjamin Yat-Ming
BY
Yung
Hsuan
H
Liu
D000818:Animals; D049109:Cell Proliferation; D002843:Chromatin / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D004275:DNA, Ribosomal / Q000235:genetics*; D004268:DNA-Binding Proteins; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation / Q000235:genetics; D020868:Gene Silencing; D006367:HeLa Cells; D056284:Histone Deacetylase 1 / Q000235:genetics; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics*; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics*; D012335:RNA, Ribosomal / Q000235:genetics*; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D014158:Transcription, Genetic
D002843:Chromatin; D004275:DNA, Ribosomal; D004268:DNA-Binding Proteins; C491719:MYBBP1A protein, human; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D012335:RNA, Ribosomal; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1