Phenotypic transcription factors epigenetically mediate cell growth control
Department of Cell Biology
Animals; Cell Differentiation; Cell Line; Cell Lineage; Cell Proliferation; DNA, Ribosomal; Down-Regulation; *Epigenesis, Genetic; Mesoderm; Mice; MyoD Protein; Myogenin; Nucleolus Organizer Region; Phenotype; Pol1 Transcription Initiation Complex Proteins; Protein Binding; Protein Biosynthesis; Protein Transport; RNA, Ribosomal; Repetitive Sequences, Nucleic Acid; Transcription Factors; Transcription, Genetic
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.
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Citation: Proc Natl Acad Sci U S A. 2008 May 6;105(18):6632-7. Epub 2008 Apr 29. Link to article on publisher's site
Proceedings of the National Academy of Sciences of the United States of America