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.
DOI of Published Version
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
Ali SA, Zaidi SK, Dacwag CS, Salma N, Young DW, Shakoori AR, Montecino MA, Lian JB, Van Wijnen AJ, Imbalzano AN, Stein GS, Stein JL. (2008). Phenotypic transcription factors epigenetically mediate cell growth control. Cell and Developmental Biology Publications. https://doi.org/10.1073/pnas.0800970105. Retrieved from https://escholarship.umassmed.edu/cellbiology_pp/84