Department of Biological Science, Florida State University, Tallahassee, FL 32306-4370, USA.
Mol Biol Cell. 2011 Jun 15;22(12):1985-96. doi: 10.1091/mbc.E10-06-0545. Epub 2011 Apr 20.
To tether sister chromatids, a protein-loading complex, including Scc2, recruits cohesin to the chromosome at discrete loci. Cohesin facilitates the formation of a higher-order chromosome structure that could also influence gene expression. How cohesin directly regulates transcription remains to be further elucidated. We report that in budding yeast Scc2 is required for sister-chromatid cohesion during meiosis for two reasons. First, Scc2 is required for activating the expression of REC8, which encodes a meiosis-specific cohesin subunit; second, Scc2 is necessary for recruiting meiotic cohesin to the chromosome to generate sister-chromatid cohesion. Using a heterologous reporter assay, we have found that Scc2 increases the activity of its target promoters by recruiting cohesin to establish an upstream cohesin-associated region in a position-dependent manner. Rec8-associated meiotic cohesin is required for the full activation of the REC8 promoter, revealing that cohesin has a positive feedback on transcriptional regulation. Finally, we provide evidence that chromosomal binding of cohesin is sufficient for target-gene activation during meiosis. Our data support a noncanonical role for cohesin as a transcriptional activator during cell differentiation.
为了固定姐妹染色单体,包括 Scc2 在内的蛋白加载复合物将黏合蛋白募集到染色体的离散位置。黏合蛋白有助于形成更高级的染色体结构,这也可能影响基因表达。黏合蛋白如何直接调控转录仍有待进一步阐明。我们报告说,在芽殖酵母中,Scc2 由于两个原因而需要在减数分裂期间保持姐妹染色单体的黏合。首先,Scc2 对于激活 REC8 的表达是必需的,后者编码一种减数分裂特异性黏合蛋白亚基;其次,Scc2 对于将减数分裂黏合蛋白招募到染色体上以产生姐妹染色单体黏合是必需的。使用异源报告基因测定,我们发现 Scc2 通过以位置依赖的方式将黏合蛋白募集到启动子上来增加其靶启动子的活性,从而建立上游黏合相关区域。Rec8 相关的减数分裂黏合蛋白对于 REC8 启动子的完全激活是必需的,这表明黏合蛋白对转录调控具有正反馈作用。最后,我们提供了证据表明,在减数分裂过程中,黏合蛋白在染色体上的结合足以激活靶基因。我们的数据支持黏合蛋白在细胞分化过程中作为转录激活因子的非典型作用。