Coustham Vincent, Bedet Cécile, Monier Karine, Schott Sonia, Karali Marianthi, Palladino Francesca
Laboratoire de Biologie Moleculaire de la Cellule, Ecole Normale Supérieure de Lyon, 69007 Lyon, France.
Dev Biol. 2006 Sep 15;297(2):308-22. doi: 10.1016/j.ydbio.2006.04.474. Epub 2006 May 23.
HP1 proteins are essential components of heterochromatin and contribute to the transcriptional repression of euchromatic genes via the recruitment to specific promoters by corepressor proteins including TIF1 and Rb. The Caenorhabditis elegans HP1 homologue HPL-2 acts in the "synMuv" (synthetic multivulval) pathway, which defines redundant negative regulators of a Ras signaling cascade required for vulval induction. Several synMuv genes encode for chromatin-associated proteins involved in transcriptional regulation, including Rb and components of the Mi-2/NuRD and TIP60/NuA4 chromatin remodeling complexes. Here, we show that HPL-2 physically interacts in vitro and in vivo with the multiple zinc finger protein LIN-13, another member of the synMuv pathway. A variant of the conserved PXVXL motif found in many HP1-interacting proteins mediates LIN-13 binding to the CSD of HPL-2. We further show by in vivo localization studies that LIN-13 is required for HPL-2 recruitment in nuclear foci. Our data suggest that the LIN-13/HPL-2 complex may physically link a subset of the Rb related synMuv proteins to chromatin.
HP1蛋白是异染色质的重要组成部分，通过包括TIF1和Rb在内的共抑制蛋白募集到特定启动子，从而有助于常染色质基因的转录抑制。秀丽隐杆线虫的HP1同源物HPL-2在“合成多阴门”（synMuv）途径中起作用，该途径定义了阴门诱导所需的Ras信号级联反应的冗余负调节因子。几个synMuv基因编码参与转录调控的染色质相关蛋白，包括Rb以及Mi-2/NuRD和TIP60/NuA4染色质重塑复合物的成分。在这里，我们表明HPL-2在体外和体内与synMuv途径的另一个成员——多锌指蛋白LIN-13发生物理相互作用。在许多与HP1相互作用的蛋白中发现的保守PXVXL基序的一个变体介导LIN-13与HPL-2的CSD结合。我们通过体内定位研究进一步表明，LIN-13是HPL-2募集到核灶所必需的。我们的数据表明，LIN-13/HPL-2复合物可能将一部分与Rb相关的synMuv蛋白与染色质物理连接起来。
