One possible role for clustering of epigenetic responses across wide areas is the coordinate regulation of a large group of functionally related genes. We discovered that the expression of a large cluster of the Pcdh genes is coordinately regulated with respect to maternal care. Remarkably, the increase in gene expression in the High maternal care group spans genes within each of the Pcdh gene clusters ( Fig. 1c ; Fig. 5a–b ). This family of genes correspondingly contains a significant overrepresentation of differentially methylated regions. It is interesting to speculate that the Pcdh gene family may have evolved though gene duplication as a class of functionally-related genes under coordinate epigenetic regulation. Indeed, coordinated silencing of the Pcdh family of genes was seen in cancer [34]. However, in cancer, processes related to cell-selection might be involved in a progressive spreading of DNA methylation [35], [36], [37].
