Molecular mechanisms of gene-specific transcriptional regulation by histone methyl transferase

异染色质是在整个细胞周期中保持浓缩的基因组部分，在S期晚期复制，并且通常与染色体的臂间区和端粒区相关。通过染色体重排或反式募集而被置于异染色质附近的常染色质基因将被抑制、沉默，这种现象被称为位置效应杂色（PEV）。多梳族蛋白（Polycomb group protein，PcG）介导的基因沉默常与异染色质介导的基因沉默进行比较，因为在PcG蛋白中观察到的一些保守结构域与HP 1共有（chromodomain）和Su（var）3-9（染色体结构域和SET结构域），也因为PcG蛋白，像PEV的修饰剂，为了阐明由SUV 39 H1-HP 1和SU（Z）12-EZH 2系统引发和/或维持异染色质的分子机制，我们研究了这些蛋白质的相互作用。我们发现1）通过HP 1的染色体阴影结构域的自身相互作用对于SUV 39 H1募集到核小体上是至关重要的2）PcG SU（Z）12直接与HP 1和EZH 2相互作用并且在HP 1存在下抑制转录。我们认为SU（Z）12通过将EZH 2或EED-EZH 2复合物募集到HP 1结合的核小体上，在异染色质和/或HP 1介导的常染色质基因转录抑制的维持中发挥作用。

Heterochromatin is the fraction of genome that remains condensed throughout the cell cycle, replicates in the late S phase, and is generally associated with pericentric and telomeric regions of chromosomes. Euchromatic genes placed into proximity of heterochromatin by chromosomal rearrangement or trans-recruitment will be variably, silenced, a phenomenon known as position effect variegation (PEV). The Polycomb group protein (PcG)-mediated gene silencing has often been compared with the heterochromatin-mediated one because some conserved domains observed in PcG proteins are shared with HP1 (chromodomain) and Su(var)3-9 (chromodomain and SET domain), and also because PcG proteins, like modifiers of PEV, are dosage sensitive.In order to elucidate molecular mechanisms of heterochromatin initiation and/or maintenance by SUV39H1-HP1 and SU(Z)12-EZH2 systems, we investigated interactions of these proteins. We found that 1) self-interaction through the chromo shadow domain of HP1 is crucial for recruitment of SUV39H1 onto nucleosomes 2) PcG SU(Z)12 directly interacts with HP1 and EZH2 and represses transcription in the presence of HP1. We suggest that a role for SU(Z)12 in the maintenance of heterochromatin and/or HP1-mediated transcriptional repression of euchromatic genes by recruiting EZH2 or EED-EZH2 complex onto HP1□-bound nucleosomes.