黏着素与基因表达调控

Cohesin in Gene Regulation

黏着素(cohesin)是一种多亚基蛋白复合体,在进化上相当保守.在真核生物细胞中,黏着素主要功能是将复制产生的姐妹染色单体连接在一起,直到细胞分裂的后期,黏着素亚基Scc1水解最终导致染色单体的分离.最近的研究表明,黏着素在基因表达、染色质结构变化和发育调节等方面也起着非常重要的作用,并且发现黏着素对基因的调节作用与其对染色体的黏着功能无关.在酵母中,黏着素最初定位于其装载蛋白Scc2的DNA结合位点上,但是在细胞周期的G2期,黏着素聚集于转录汇集区之间进而调控转录终止.在果蝇染色体上,黏着素与装载蛋白Scc2的同源物Nipped-B共定位,其作用是阻抑增强子和启动子的远距离接触.而在哺乳动物中,黏着素与CTCF隔离子蛋白共定位,并以依赖于CTCF的方式调控转录.本文概述了黏着素在不同真核生物染色体上的定位与分布,并对其在基因表达调控中的功能机制及其研究现状进行了重点阐述.

Cohesin is an evolutionally conserved multisubunit complex. In eukaryotic cells, its main function, which depends on the proteolytic cleavage of cohesin subunit Sccl, is to hold replicated sister chromatids together until their segregation at anaphase. Recent studies in yeast and different animal species have shown cohesin also involved in gene regulation, chromatin structure and development. The functions of cohesin in gene expression regulation seemed to be independent to its role in cell cohesion. Cohesin is initially loaded onto the chromosomes in yeast at the sites occupied by the Scc2/4 loader protein, then accumulates between convergent genes in G2 phase of the cell cycle and mediates transcription termination. In Drosophila, cohesin mostly stays close to its loader Nipped-B, and inhibits long-range enhancer-promoter interactions. Finally, in mammals, cohesin co-localizes with the CTCF insulator protein and controls gene expression in a CTCF- dependent manner. This review will focus on the various targeting mechanisms and the gene regulatory functions of cohesin in different eukaryotes.