Phenotypic transcription factors epigenetically mediate cell growth control

Syed A. Ali, Sayyed K. Zaidi, Caroline S. Dacwag, Nunciada Salma, Daniel W. Young, Abdul R. Shakoori, Martin A. Montecino, Jane B. Lian, Andre J. Van Wijnen, Anthony N. Imbalzano, Gary S. Stein, Janet L. Stein

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

Ribosomal RNA (rRNA) genes are down-regulated during osteogenesis, myogenesis, and adipogenesis, necessitating a mechanistic understanding of interrelationships between growth control and phenotype commitment. Here, we show that cell fate-determining factors [MyoD, myogenin (Mgn) , Runx2, C/EBPβ] occupy rDNA loci and suppress rRNA expression during lineage progression, concomitant with decreased rRNA expression and reciprocal loss of occupancy by c-Myc, a proliferation-specific activator of rRNA transcription. We find interaction of phenotypic factors with the polymerase I activator upstream binding factor UBF-1 at interphase nucleoli, and this interaction is epigenetically retained on mitotic chromosomes at nucleolar organizing regions. Ectopic expression and RNA interference establish that MyoD, Mgn, Runx2, and C/EBPβ each functionally suppress rRNA genes and global protein synthesis. We conclude that epigenetic control of ribosomal biogenesis by lineage-specific differentiation factors is a general developmental mechanism for coordinate control of cell growth and phenotype.

Original languageEnglish (US)
Pages (from-to)6632-6637
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number18
DOIs
StatePublished - May 6 2008

Keywords

  • C/EBP
  • Mitosis
  • MyoD
  • Runx

ASJC Scopus subject areas

  • General

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  • Cite this

    Ali, S. A., Zaidi, S. K., Dacwag, C. S., Salma, N., Young, D. W., Shakoori, A. R., Montecino, M. A., Lian, J. B., Van Wijnen, A. J., Imbalzano, A. N., Stein, G. S., & Stein, J. L. (2008). Phenotypic transcription factors epigenetically mediate cell growth control. Proceedings of the National Academy of Sciences of the United States of America, 105(18), 6632-6637. https://doi.org/10.1073/pnas.0800970105