A Runx2-HDAC1 co-repressor complex regulates rRNA gene expression by modulating UBF acetylation
Copyright policy )A Runx2-HDAC1 co-repressor complex regulates rRNA gene expression by modulating UBF acetylation
The osteogenic and oncogenic transcription factor Runx2 downregulates expression of RNA Pol I-mediated rRNA genes and changes histone modifications associated with the rDNA repeat. However, the mechanisms by which Runx2 suppresses rRNA transcription are not well understood. Runx2 co-factors such as histone deacetylases (HDACs) play a key role in chromatin remodeling and regulation of gene transcription. Here we show that Runx2 recruits HDAC1 to the rDNA repeats in osseous cells. This recruitment alters the histone modifications associated with active rRNA genes and causes deacetylation of Upstream Binding Factor (UBF). Downregulation of Runx2 expression reduces localization of HDAC1 at the nucleolar periphery and also decreases HDAC1 association with UBF. Functionally, depletion of HDAC1 relieves Runx2-mediated rRNA gene repression concomitant with increased cell proliferation and global protein synthesis in osseous cells. Our findings collectively identify a Runx2-HDAC1 dependent mechanism for the regulation of rRNA genes and suggest plasticity to Runx2-mediated epigenetic control through selective mitotic exclusion of co-regulatory factors.
- University of Massachusetts Medical School United States
Core Binding Factor Alpha 1 Subunit, Histone Deacetylase 1, DNA, Ribosomal, Cell Line, Histones, Humans, Interphase, Cell Proliferation, Ribosomal, Acetylation, DNA, Cell Biology, Chromatin, Protein Transport, Gene Expression Regulation, Genetic Loci, RNA, Ribosomal, Gene Knockdown Techniques, Protein Biosynthesis, Co-Repressor Proteins, Pol1 Transcription Initiation Complex Proteins, Cell Nucleolus, Protein Binding
Core Binding Factor Alpha 1 Subunit, Histone Deacetylase 1, DNA, Ribosomal, Cell Line, Histones, Humans, Interphase, Cell Proliferation, Ribosomal, Acetylation, DNA, Cell Biology, Chromatin, Protein Transport, Gene Expression Regulation, Genetic Loci, RNA, Ribosomal, Gene Knockdown Techniques, Protein Biosynthesis, Co-Repressor Proteins, Pol1 Transcription Initiation Complex Proteins, Cell Nucleolus, Protein Binding
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