A RUNX2-HDAC1 co-repressor complex regulates rrna gene expression by modulating UBF acetylation

Syed A. Ali, Jason R. Dobson, Jane B. Lian, Janet L. Stein, Andre J van Wijnen, Sayyed K. Zaidi, Gary S. Stein

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The osteogenic and oncogenic transcription factor RUNX2 downregulates the RNA polymerase I (RNA Pol I)-mediated transcription of rRNAs and changes histone modifications associated with the rDNA repeat. However, the mechanisms by which RUNX2 suppresses rRNA transcription are not well understood. RUNX2 cofactors 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-encoding genes and causes deacetylation of the protein upstream binding factor (UBF, also known as UBTF). Downregulation of RUNX2 expression reduces the localization of HDAC1 to the nucleolar periphery and also decreases the association between HDAC1 and UBF. Functionally, depletion of HDAC1 relieves the RUNX2-mediated repression of rRNA-encoding genes and concomitantly increases cell proliferation and global protein synthesis in osseous cells. Our findings collectively identify a RUNX2-HDAC1-dependent mechanism for the regulation of rRNA-encoding genes and suggest that there is plasticity to RUNX2-mediated epigenetic control, which is mediated through selective mitotic exclusion of co-regulatory factors.

Original languageEnglish (US)
Pages (from-to)2732-2739
Number of pages8
JournalJournal of Cell Science
Volume125
Issue number11
DOIs
StatePublished - Jun 1 2012
Externally publishedYes

Fingerprint

Co-Repressor Proteins
Acetylation
Histone Code
rRNA Genes
Ribosomal DNA
Gene Expression
Down-Regulation
RNA Polymerase I
Histone Deacetylases
Chromatin Assembly and Disassembly
Protein Binding
Epigenomics
Transcription Factors
Cell Proliferation
Genes
Proteins

Keywords

  • Hdac1
  • Histone acetylation
  • Nucleolus
  • Osseous cell
  • RNA polymerase I
  • RRNA
  • Runx2

ASJC Scopus subject areas

  • Cell Biology

Cite this

Ali, S. A., Dobson, J. R., Lian, J. B., Stein, J. L., van Wijnen, A. J., Zaidi, S. K., & Stein, G. S. (2012). A RUNX2-HDAC1 co-repressor complex regulates rrna gene expression by modulating UBF acetylation. Journal of Cell Science, 125(11), 2732-2739. https://doi.org/10.1242/jcs.100909

A RUNX2-HDAC1 co-repressor complex regulates rrna gene expression by modulating UBF acetylation. / Ali, Syed A.; Dobson, Jason R.; Lian, Jane B.; Stein, Janet L.; van Wijnen, Andre J; Zaidi, Sayyed K.; Stein, Gary S.

In: Journal of Cell Science, Vol. 125, No. 11, 01.06.2012, p. 2732-2739.

Research output: Contribution to journalArticle

Ali, SA, Dobson, JR, Lian, JB, Stein, JL, van Wijnen, AJ, Zaidi, SK & Stein, GS 2012, 'A RUNX2-HDAC1 co-repressor complex regulates rrna gene expression by modulating UBF acetylation', Journal of Cell Science, vol. 125, no. 11, pp. 2732-2739. https://doi.org/10.1242/jcs.100909
Ali SA, Dobson JR, Lian JB, Stein JL, van Wijnen AJ, Zaidi SK et al. A RUNX2-HDAC1 co-repressor complex regulates rrna gene expression by modulating UBF acetylation. Journal of Cell Science. 2012 Jun 1;125(11):2732-2739. https://doi.org/10.1242/jcs.100909
Ali, Syed A. ; Dobson, Jason R. ; Lian, Jane B. ; Stein, Janet L. ; van Wijnen, Andre J ; Zaidi, Sayyed K. ; Stein, Gary S. / A RUNX2-HDAC1 co-repressor complex regulates rrna gene expression by modulating UBF acetylation. In: Journal of Cell Science. 2012 ; Vol. 125, No. 11. pp. 2732-2739.
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