CTCF-dependent chromatin insulator is linked to epigenetic remodeling
CTCF-dependent chromatin insulator is linked to epigenetic remodeling
复制标题
DOI：
10.1016/j.molcel.2006.08.008
复制
发表时间：
2006-09-01
期刊：
影响因子：
16
通讯作者：
Nakao, Mitsuyoshi
中科院分区：
文献类型：
--
作者：
Ishihara, Ko;Oshimura, Mitsuo;Nakao, Mitsuyoshi
染色质绝缘子是相邻染色体区域之间的边界元件，它们通过以位置依赖性方式阻断附近增强子的作用来发挥作用。在这里，我们表明，SNF 2样chromodomain解旋酶蛋白质CHD 8与绝缘子结合蛋白CTCF相互作用。染色质免疫沉淀分析显示，CHD 8存在于已知的CTCF靶位点，如H19的差异甲基化区域（DMR），β-珠蛋白的基因座控制区域，以及BRCA 1和c-myc基因的启动子区域。RNA干扰介导的CHD 8敲低显著消除了高度依赖于CTCF的H19 DMR绝缘子活性，导致来自母体来源的染色体的印迹IGF 2的重新激活。此外，CHD 8的缺乏影响BRCA 1和c-myc基因的CTCF结合位点周围的CpG甲基化和组蛋白乙酰化，邻近异染色质。这些发现提供了深入了解CTCF-CHD 8复合物在活性绝缘子位点的绝缘和表观遗传调节中的作用。
Chromatin insulators are boundary elements between distinctly regulated, neighboring chromosomal domains, and they function by blocking the effects of nearby enhancers in a position-dependent manner. Here, we show that the SNF2-like chromodomain helicase protein CHD8 interacts with the insulator binding protein CTCF. Chromatin immunoprecipitation analysis revealed that CHD8 was present at known CTCF target sites, such as the differentially methylated region (DMR) of H19, the locus control region of beta-globin, and the promoter region of BRCA1 and c-myc genes. RNA interference-mediated knockdown of CHD8 significantly abolished the H19 DMR insulator activity that depends highly on CTCF, leading to reactivation of imprinted IGF2 from chromosome of maternal origin. Further, the lack of CHD8 affected CpG methylation and histone acetylation around the CTCF binding sites, adjacent to heterochromatin, of BRCA1 and c-myc genes. These findings provide insight into the role of CTCF-CHD8 complex in insulation and epigenetic regulation at active insulator sites.