GSBS Student Publications

Phenotypic transcription factors epigenetically mediate cell growth control

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

Document Type Article

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/EBPbeta] 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/EBPbeta 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.