Eskeland Ragnhild, Eberharter Anton, Imhof Axel
Histone Modifications Group, Adolf-Butenandt Institut, University of Munich, Schillerstrasse 44, 80336 Munich, Germany.
Mol Cell Biol. 2007 Jan;27(2):453-65. doi: 10.1128/MCB.01576-06. Epub 2006 Nov 13.
A large portion of the eukaryotic genome is packaged into transcriptionally silent heterochromatin. Several factors that play important roles during the establishment and maintenance of this condensed form have been identified. Methylation of lysine 9 within histone H3 and the subsequent binding of the chromodomain protein heterochromatin protein 1 (HP1) are thought to initiate heterochromatin formation in vivo and to propagate a heterochromatic state lasting through several cell divisions. For the present study we analyzed the binding of HP1 to methylated chromatin in a fully reconstituted system. In contrast to its strong binding to methylated peptides, HP1 binds only weakly to methylated chromatin. However, the addition of recombinant SU(VAR) protein, such as ACF1 or SU(VAR)3-9, facilitates HP1 binding to chromatin methylated at lysine 9 within the H3 N terminus (H3K9). We propose that HP1 has multiple target sites that contribute to its recognition of chromatin, only one of them being methylated at H3K9. These findings have implications for the mechanisms of recognition of specific chromatin modifications in vivo.
真核生物基因组的很大一部分被包装成转录沉默的异染色质。已经鉴定出了几种在这种浓缩形式的建立和维持过程中起重要作用的因子。组蛋白H3中赖氨酸9的甲基化以及随后色域蛋白异染色质蛋白1（HP1）的结合被认为在体内启动异染色质形成，并传播持续几个细胞分裂的异染色质状态。在本研究中，我们在一个完全重构的系统中分析了HP1与甲基化染色质的结合。与其与甲基化肽的强结合相反，HP1与甲基化染色质的结合较弱。然而，添加重组SU(VAR)蛋白，如ACF1或SU(VAR)3-9，可促进HP1与H3 N末端赖氨酸9（H3K9）处甲基化的染色质结合。我们提出，HP1有多个有助于其识别染色质的靶位点，其中只有一个在H3K9处被甲基化。这些发现对体内特异性染色质修饰的识别机制具有启示意义。
