Pcdh genes are predominantly expressed in neurons at synaptic junctions, and the assembly of these cell surface proteins is regulated by differential promoter activation and alternative pre-mRNA splicing [31]. Although the mechanisms underlying differential promoter activation are not well understood, promoter DNA methylation and histone acetylation play a role in Pcdh gene silencing [32], [33]. Consistent with this hypothesis, Pcdh gene expression induced in response to High LG maternal care is accompanied by higher in exonic H3K9 acetylation and DNA methylation (P<1×10−300 for both by Wilcoxon rank sum test) and lower proximal promoter DNA methylation in a majority (17 of 23, or 74%) of Pcdh genes showing a significant increase in expression among High LG compared to Low LG offspring ( Fig. 5 ). High LG offspring show a significant increase in transcription in 20 Pcdh of 33 genes profiled within the Pcdh gene clusters (Table S1). Taken together, these results showing a transcriptional and epigenetic response to maternal care across the Pcdh gene family suggest that the epigenomic response to maternal care may act coordinately on a family of genes localized in the same broad genomic region.
