Fig. 2: EDC exposure hijacks age-related epigenomic plasticity to accelerate epigenomic aging.

a Venn diagrams for increased H3K4me1 focused on histone modifications associated with target genes, defined as having differential peak calls within ±3 kb of the transcriptional start site (TSS), using the GENCODE gene model and the BEDTOOLS software (N = 3 biologically independent animals per timepoint/treatment). b Integrated genome viewer (IGV) showing representative examples of each type of reprogramming for increased H3K4me1 at target genes: Precocious Reprogramming illustrated by Adcy1, EDC-specific Reprogramming illustrated by Nudt2, and Cumulative Reprogramming illustrated by Egr1. The data shown on the y-axis are the ChIP-seq read counts normalized to 1 million mapped reads. c Circos plots of differential peaks identified by chromatin immunoprecipitation sequencing (ChIP-seq) at target genes for active and repressive epigenetic histone modifications. Epigenomic data were analyzed using the rn6 rat genome build and the latest GENCODE gene model. For each of the four histone modifications, differential peaks that distinguished EDC (N = 3 per timepoint) from vehicle (N = 3 biologically independent animals per timepoint) exposed neonates (PND5) and adults (D70) were identified using DiffReps, with significance achieved at q < 0.01 and fold change exceeding 2×. Peaks with enrichment of the histone mark are indicated in red, while peaks with loss of the histone mark are indicated in blue.