MECP2 binds the STAT5A gene

Expression of STAT5A is abrogated in cells expressing NPM1-ALK fusions by high levels of promoter methylation. Hypermethylation of the STAT5A enhancer provides binding sites for the methyl binding protein MeCP2 as assessed by chromatin immunoprecipitation, and precludes binding of the normal transcriptional activator Sp1. As a consequence of these events, STAT5A expression is repressed in NPM1-ALK + T-cell lymphomas. siRNA-mediated depletion of the NPM1-ALK effector STAT3 restores STAT5A expression in these cells, highlighting the role for STAT3 in NPM-ALK-mediated oncogenesis (Zhang et al, 2007; Zhang et al, 2002).

STAT5A基因的表达在表达NPM1-ALK融合蛋白的细胞中由于启动子的高甲基化而被抑制。通过对STAT5A增强子的超甲基化进行检测，发现其提供了甲基结合蛋白MeCP2的结合位点，并通过染色质免疫沉淀技术评估，同时阻止了正常转录激活因子Sp1的结合。因此，在NPM1-ALK阳性T细胞淋巴瘤中，STAT5A的表达受到抑制。通过siRNA介导的NPM1-ALK效应因子STAT3的降解，能够恢复这些细胞中的STAT5A表达，突显了STAT3在NPM-ALK介导的肿瘤发生过程中的作用（Zhang et al, 2007; Zhang et al, 2002）。