Paro R, Strutt H, Cavalli G
Zentrum für Molekular Biologie der Universität Heidelberg, D-69120 Heidelberg, Germany.
Novartis Found Symp. 1998;214:51-61; discussion 61-6, 104-13. doi: 10.1002/9780470515501.ch4.
In Drosophila the Polycomb group (PcG) and trithorax group (trxG) genes are required to maintain differential expression patterns of many important developmental regulatory genes. The PcG is responsible for heritable silencing throughout development. At target genes PcG response elements (PREs) attract PcG protein complexes and induce the formation of higher-order chromatin structures. We have mapped the distribution of Polycomb and other PcG members at various target genes by using an improved formaldehyde cross-linking and chromatin immunoprecipitation technique. We find that Polycomb spreads locally from PREs over several kilobases, thereby probably stabilizing the silencing complexes. Members of the trxG co-localize at PREs. GAGA factor was found to be constitutively bound to PREs independently of gene activity. PREs associated with active genes appear to have increased amounts of bound GAGA. We have developed a system capable of switching a PRE between the on/off modes. PREs and trxG-regulated elements are common chromosomal elements through which the proteins of the PcG/trxG exert their maintenance function on adjacent chromatin structures.
在果蝇中,多梳蛋白组(PcG)和三胸蛋白组(trxG)基因对于维持许多重要发育调控基因的差异表达模式是必需的。PcG负责在整个发育过程中的可遗传沉默。在靶基因处,PcG反应元件(PREs)吸引PcG蛋白复合物并诱导高阶染色质结构的形成。我们通过使用改进的甲醛交联和染色质免疫沉淀技术,绘制了多梳蛋白及其他PcG成员在各种靶基因上的分布。我们发现多梳蛋白从PREs局部扩散数千碱基,从而可能稳定沉默复合物。trxG成员共定位于PREs。发现GAGA因子与PREs组成性结合,与基因活性无关。与活性基因相关的PREs似乎结合的GAGA量增加。我们开发了一个能够在开/关模式之间切换PRE的系统。PREs和trxG调控元件是常见的染色体元件,通过它们,PcG/trxG蛋白对相邻染色质结构发挥其维持功能。