Phenotypic transcription factors epigenetically mediate cell growth control

被引:73
作者
Ali, Syed A. [1 ]
Zaidi, Sayyed K. [1 ]
Dacwag, Caroline S. [1 ]
Salma, Nunciada [1 ]
Young, Daniel W. [1 ]
Shakoori, Abdul R. [1 ]
Montecino, Martin A. [2 ]
Lian, Jane B. [1 ]
van Wijnen, Andre J. [1 ]
Imbalzano, Anthony N. [1 ]
Stein, Gary S. [1 ]
Stein, Janet L. [1 ]
机构
[1] Univ Massachusetts, Sch Med, Dept Cell Biol & Canc Ctr, Worcester, MA 01655 USA
[2] Univ Concepcion, Fac Ciencias Biol, Dept Bioquim & Biol Mol, Concepcion, Chile
关键词
C/EBP; mitosis; MyoD; Runx;
D O I
10.1073/pnas.0800970105
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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/EBP beta] 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/EBP beta 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.
引用
收藏
页码:6632 / 6637
页数:6
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