Intergenic and intronic DNA hypomethylated regions as putative regulators of imprinted domains

To investigate the regulatory potential of intergenic/intronic hypomethylated regions (iHMRs) within imprinted domains. Based on the preliminary results of the histone modification and conservation profiles, we conducted reporter assays on the and domain iHMRs. The results were confirmed by the deletion of -iHMR designed to test its function in the imprinted domain. Initial bioinformatic analyses suggested that some iHMRs may be noncanonical enhancers for imprinted genes. Consistent with this, - and -iHMRs showed context-dependent promoter and enhancer activity. Further, deletion of -iHMR resulted in allele- and sex-specific misregulation of several imprinted genes within the domain. Taken together, these results suggest that some iHMRs may function as domain-wide regulators for the associated imprinted domains.