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首页> 外文期刊>Molecular and Cellular Biology >Dosage-Sensitive Regulation of Cohesin Chromosome Binding and Dynamics by Nipped-B, Pds5, and Wapl
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Dosage-Sensitive Regulation of Cohesin Chromosome Binding and Dynamics by Nipped-B, Pds5, and Wapl

机译：Nipped-B，Pds5和Wapl对黏附素染色体结合和动力学的剂量敏感性调节

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The cohesin protein complex holds sister chromatids together to ensure proper chromosome segregation upon cell division and also regulates gene transcription. Partial loss of the Nipped-B protein that loads cohesin onto chromosomes, or the Pds5 protein required for sister chromatid cohesion, alters gene expression and organism development, without affecting chromosome segregation. Knowing if a reduced Nipped-B or Pds5 dosage changes how much cohesin binds chromosomes, or the stability with which it binds, is critical information for understanding how cohesin regulates transcription. We addressed this question by in vivo fluorescence recovery after photobleaching (FRAP) with Drosophila salivary glands. Cohesin, Nipped-B, and Pds5 all bind chromosomes in both weak and stable modes, with residence half-lives of some 20 seconds and 6 min, respectively. Reducing the Nipped-B dosage decreases the amount of stable cohesin without affecting its chromosomal residence time, and reducing the Pds5 dosage increases the amount of stable cohesin. This argues that Nipped-B and Pds5 regulate transcription by controlling how much cohesin binds DNA in the stable mode, and not binding affinity. We also found that Nipped-B, Pds5, and the Wapl protein that interacts with Pds5 all play unique roles in cohesin chromosome binding.
机译：粘着蛋白复合物将姐妹染色单体结合在一起，以确保细胞分裂后染色体正确分离，并调节基因转录。将粘着蛋白加载到染色体上的Nipped-B蛋白或姐妹染色单体凝聚所需的Pds5蛋白的部分丢失，可以改变基因表达和生物发育，而不会影响染色体分离。知道减少的Nipped-B或Pds5剂量是否会改变黏附素与染色体的结合量或与染色体结合的稳定性，对于了解黏附素如何调节转录至关重要。我们用果蝇唾液腺进行光漂白（FRAP）后，通过体内荧光恢复来解决这个问题。 Cohesin，Nipped-B和Pds5均以弱和稳定模式结合染色体，其滞留半衰期分别为20秒和6分钟。减少Nipped-B剂量可减少稳定黏附素的量，而不影响其染色体停留时间，而减少Pds5剂量可增加稳定黏附素的量。这表明Nipped-B和Pds5通过控制在稳定模式下结合DNA的黏聚素的数量而不是亲和力来调控转录。我们还发现，Nipped-B，Pds5和与Pds5相互作用的Wapl蛋白在黏附素染色体结合中均发挥独特作用。

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