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.