Fig. 2

Fetal-neonatal ID and prenatal choline supplementation altered histone H3K9me3 landscape in P65 FID rat hippocampus. A H3K9me3 ChIP-seq data showing differential sites and associated genes between treatment groups. Numbers of differential sites include gene bodies, promoter regions (proximal, + 1 K, + 3 K), and intergenic regions. Selection criteria were absolute log2(Fold Change) > 0.2 and false discovery rate q-value < 0.05, n = 4/group. B Distribution of sites with differential H3K9me3 enrichment. (C, D) Ingenuity Pathway Analysis (IPA) mapped differentially-enriched H3K9me3 loci onto biofunctions (C) and canonical signaling pathways (D), ranked hierarchically. Comparisons were made among formerly iron-deficient (FID), formerly iron-deficient with choline (FIDch), and iron-sufficient with choline (ISch) normalized by the iron-sufficient (IS) control group. Squares with dots have absolute z-scores < 2.0. Blue and orange colors indicate decreased and increased H3K9me3 enrichment, respectively. Early-life ID produced little changes in H3K9me3 signature (absolute z-scores < 2.0). Choline increased H3K9me3 enrichment in the FIDch and ISch groups. E Venn diagram showing overlap and non-overlapping genes modified in FID and FIDch groups. +/−/n indicate increased, decreased, and normalized changes in H3K9me3. Blue and orange indicate decreased and increased H3K9me3 signatures. F Comparison between ISch and IS control group showing the choline effect on H3K9me3 in adult rat hippocampus. IPA generates a graphical summary showing increased H3K9me3 in loci associated with cognition and estrogen receptor signaling, and canonical pathways showing significantly increased H3K9me3 enrichment