Phenotypic transcription factors epigenetically mediate cell growth control
Phenotypic transcription factors epigenetically mediate cell growth control
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DOI：
10.1073/pnas.0800970105
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发表时间：
2008-05-06
影响因子：
11.1
通讯作者：
Stein, Janet L.
中科院分区：
文献类型：
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作者：
Ali, Syed A.;Zaidi, Sayyed K.;Stein, Janet L.
核糖体RNA （rRNA）基因在骨形成、肌肉形成和脂肪形成过程中下调，因此需要对生长控制和表型承诺之间的相互关系进行机制理解。在这里，我们发现细胞命运决定因子[MyoD， myogenin (Mgn), Runx2， C/EBP β]在谱系进展中占据rDNA位点并抑制rRNA表达，同时伴随着rRNA表达降低和C - myc（一种增殖特异性rRNA转录激活因子）占用的相互丧失。我们发现表型因子与间期核核中聚合酶I激活因子上游结合因子UBF-1的相互作用，并且这种相互作用在有丝分裂染色体的核核组织区被表观遗传地保留。异位表达和RNA干扰证实MyoD、Mgn、Runx2和C/EBP β都能抑制rRNA基因和全局蛋白合成。我们得出结论，通过谱系特异性分化因子对核糖体生物发生的表观遗传控制是协调控制细胞生长和表型的一般发育机制。
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.