Effects of sister chromatid cohesion proteins on cut gene expression during wing development in Drosophila
Effects of sister chromatid cohesion proteins on cut gene expression during wing development in Drosophila
复制标题
DOI：
10.1242/dev.02064
复制
发表时间：
2005-11-01
期刊：
影响因子：
4.6
通讯作者：
McKim, K
中科院分区：
文献类型：
--
作者：
Dorsett, D;Eissenberg, JC;McKim, K
粘连蛋白复合物是染色体的保守结构成分。粘连蛋白沿着间期染色体结合许多位点，对于姐妹染色单体的粘连和 DNA 修复至关重要。在这里，我们测试了粘连蛋白也调节基因表达的想法。这个想法源于这样的发现：果蝇 Nipped-B 蛋白是酵母 Scc2 因子的功能同源物，可将粘连蛋白加载到染色体上，通过位于距启动子数千碱基的增强子促进某些基因的转录激活。我们发现，在培养细胞中，粘连蛋白结合在远程翼缘增强子和切割位点处的启动子之间，并且减少 Smcl 粘连蛋白亚基的剂量会增加发育中翼缘的切割表达。我们还发现，独特的 pds5 基因突变减少了粘连蛋白与染色体的结合，从而增加了剪切表达。基于这些结果，我们假设粘连蛋白抑制果蝇剪切基因的远程激活，而 Nipped-B 通过调节粘连蛋白-染色体结合来促进激活。粘连蛋白对基因表达的这种影响可能是 Cornelia de Lange 综合征中发生的许多发育缺陷的原因，该综合征是由 Nipped-B 的人类同源物突变引起的。
The cohesin protein complex is a conserved structural component of chromosomes. Cohesin binds numerous sites along interphase chromosomes and is essential for sister chromatid cohesion and DNA repair. Here, we test the idea that cohesin also regulates gene expression. This idea arose from the finding that the Drosophila Nipped-B protein, a functional homolog of the yeast Scc2 factor that loads cohesin onto chromosomes, facilitates the transcriptional activation of certain genes by enhancers located many kilobases away from their promoters. We find that cohesin binds between a remote wing margin enhancer and the promoter at the cut locus in cultured cells, and that reducing the dosage of the Smcl cohesin subunit increases cut expression in the developing wing margin. We also find that cut expression is increased by a unique pds5 gene mutation that reduces the binding of cohesin to chromosomes. On the basis of these results, we posit that cohesin inhibits long-range activation of the Drosophila cut gene, and that Nipped-B facilitates activation by regulating cohesin-chromosome binding. Such effects of cohesin on gene expression could be responsible for many of the developmental deficits that occur in Cornelia de Lange syndrome, which is caused by mutations in the human homolog of Nipped-B.