Fig. 3: Transcriptional profiling reveals reprogramming of the EGR1 transcriptome.

a Transcriptomic profiling by RNA-seq of vehicle- (VEH black bar) and EDC- (EDC red bar) exposed livers animals fed a Western-style diet. N = 3 biologically independent animals per treatment. Heatmap showing DEseq differential gene analysis, with significance achieved at q-value < 0.1 and fold change exceeding 1.25×. b Overrepresentation analysis (ORA) of differentially expressed genes performed using a hypergeometric test, with significance achieved at q < 0.2, against the Hallmark gene set compendium and the GO database. c Volcano plot of the transcriptomic footprint from EDC-exposed vs VEH-exposed livers of animals fed a Western-style diet. Red circles indicate upregulated, while blue circles indicate downregulated genes, respectively. Larger circles identify the top 20 up- and downregulated genes. d Reprogramming of histone marks for Egr1 illustrates Precocious Reprogramming of H3K4me1 and Cumulative Reprogramming of H3K27me3 shown with IGV browser plots using ChIP-seq data obtained at PND5 (upper) and D70 (lower). e RT-qPCR analysis of Egr1 gene expression in the liver of animals at PND5, D70, or D240 after feeding a Western-style diet. Vehicle (VEH) = black dots, EDC = red dots. N = 9 biologically independent animals for VEH and N = 10 biologically independent animals for EDC. The p value generated by t test is indicated. *p < 0.05. f Western analysis for EGR1 expression in EDC- vs VEH-exposed livers (left) and quantitation (right). N = 9 biologically independent animals for VEH and N = 10 biologically independent animals for EDC. The p value generated by t test is indicated. ****p < 0.0001. g EGR1 targets within the significant differentially expressed gene signature (a) were identified using the Harmonizome database (‘All’ shown with gray bars). EGR1 targets are represented as total gene number (left) or as the percent of the differentially expressed genes (right). Genes that were increased are represented as ‘Up’, and genes that were decreased in the EDC signature are represented as ‘Down’. Source data for a, b and e–g are provided as a Source data file.