Our approach using high-density tiling microarrays also provided us with a “macroscopic” perspective of the epigenetic and transcriptional responses to maternal care. By zooming out of the specific suspected regions, we discovered differentially-methylated and acetylated regions that span large domains of sequence in the vicinity of the NR3C1 gene ( Fig. 4a ). Among adult offspring of animals that had received relatively low levels of maternal care, we identified several hypermethylated RDme and hyperacetylated RDac upstream of the 5′ NR3C1 exon variants as well as in intronic regions, where transcription was also detected. These results suggest the possible involvement of non-coding RNAs and alternative splice variants in response to maternal care. Future studies are required to determine whether these broad regions that are differentially methylated in response to maternal care regulate NR3C1 expression.
