Department of Molecular Biology and Biochemistry, Rutgers University, 604 Allison Road, Piscataway, NJ 08854, USA.
Mech Dev. 2012 Jan-Feb;128(11-12):536-47. doi: 10.1016/j.mod.2012.01.004. Epub 2012 Jan 24.
Certain Polycomb group (PcG) genes are themselves targets of PcG complexes. Two of these constitute the Drosophila Psc-Su(z)2 locus, a region whose chromatin is enriched for H3K27me3 and contains several putative Polycomb response elements (PREs) that bind PcG proteins. To understand how PcG mechanisms regulate this region, the repressive function of the PcG protein binding sites was analyzed using reporter gene constructs. We find that at least two of these are functional PREs that can silence a reporter gene in a PcG-dependent manner. One of these two can also display anti-silencing activity, dependent on the context. A PcG protein binding site near the Psc promoter behaves not as a silencer but as a down-regulation module that is actually stimulated by the Pc gene product but not by other PcG products. Deletion of one of the PREs increases the expression level of Psc and Su(z)2 by twofold at late embryonic stages. We present evidence suggesting that the Psc-Su(z)2 locus is flanked by insulator elements that may protect neighboring genes from inappropriate silencing. Deletion of one of these regions results in extension of the domain of H3K27me3 into a region containing other genes, whose expression becomes silenced in the early embryo.
某些 Polycomb 组 (PcG) 基因本身就是 PcG 复合物的靶标。其中两个构成了果蝇 Psc-Su(z)2 基因座，该区域的染色质富含 H3K27me3，并包含几个假定的 PcG 反应元件 (PREs)，这些元件结合 PcG 蛋白。为了了解 PcG 机制如何调节这个区域，使用报告基因构建体分析了 PcG 蛋白结合位点的抑制功能。我们发现，其中至少有两个是功能性 PREs，可以以 PcG 依赖的方式沉默报告基因。这两个中的一个也可以显示抗沉默活性，这取决于上下文。Psc 启动子附近的一个 PcG 蛋白结合位点不作为沉默子，而是作为下调模块，实际上受到 Pc 基因产物的刺激，但不受其他 PcG 产物的刺激。删除一个 PRE 会使晚期胚胎阶段 Psc 和 Su(z)2 的表达水平增加两倍。我们提供的证据表明，Psc-Su(z)2 基因座由绝缘子元件环绕，这些绝缘子元件可能保护相邻基因免受不当沉默。删除其中一个区域会导致 H3K27me3 进入包含其他基因的区域，这些基因的表达在早期胚胎中沉默。
