Department of Biological Sciences, Lehigh University, Bethlehem, PA, USA.
Cell Cycle. 2010 Apr 15;9(8):1601-6. doi: 10.4161/cc.9.8.11307.
Cohesion factors pair together sister chromatids from early S-phase until anaphase onset. Numerous findings also establish an additional role in transcription. In humans, mutations in cohesion factors result in developmental abnormalities such as Cornelia de Lange, Roberts Syndrome/SC-Phocomelia, Rothman-Thompson Syndrome and others. While clinically relevant, a detailed study that links experimentally-defined cohesin defects to transcriptional changes remains lacking. Here, we report on the effects of cohesin inactivation during an early and discrete portion of the cell cycle. Even transient cohesin inactivation during the G1 portion of the cell cycle results in significant and reproducible changes in transcription. Surprisingly, over a third of the affected genes exhibit inter-related functions, suggesting that cohesin positioning along chromosomes evolved to coordinate gene expression. Prior studies indicate that defects in rRNA maturation/ribosome biogenesis produce developmental maladies in humans. Thus, the identification of genes critical for rRNA maturation in this study is of particular interest.
黏合因子将姐妹染色单体配对,从早期 S 期到后期起始。许多研究结果还确立了它们在转录中的额外作用。在人类中,黏合因子的突变会导致发育异常,如 Cornelia de Lange、Roberts 综合征/SC-短肢畸形、Rothman-Thompson 综合征等。虽然具有临床相关性,但缺乏将实验定义的黏合缺陷与转录变化联系起来的详细研究。在这里,我们报告了在细胞周期的早期和离散部分失活黏合因子的影响。即使在细胞周期的 G1 部分短暂失活黏合因子,也会导致转录发生显著且可重复的变化。令人惊讶的是,超过三分之一受影响的基因表现出相互关联的功能,这表明沿着染色体定位的黏合因子的进化是为了协调基因表达。先前的研究表明,rRNA 成熟/核糖体生物发生的缺陷会导致人类发育障碍。因此,本研究中鉴定出对 rRNA 成熟至关重要的基因特别有趣。