GSE104401
ERa Dependent Alterations in the Epigenetic Landscape of the Mouse Uterus Following Neonatal Estrogen Exposure [ChIP-Seq]
Abstract. Very little is known regarding how hormonal exposures impact the epigenetic landscape of developing tissues in the context of a whole organism, in contrast to the impact on cultured cells. Here we took a global approach to understanding how neonatal exposure to the xenoestrogen, diethylstilbestrol (DES), alters the uterine epigenome. RNA-seq and ChIP-seq (H3K4me3, H3K27me3, H3K27ac and H3K4me1) were performed on DES-treated and control uteri. The most striking finding was differential association of H3K27ac and H3K4me1 at typical and super-enhancer regions of 79% of altered genes. These peaks overlapped with previously reported estrogen receptor a (ERa) ChIP-seq peaks. Conditional uterine deletion of ERa (Esr1cKO) conferred protection of 88% of altered genes. H3K27ac ChIP-seq on Esr1cKO samples showed that 72% of protected genes had a differential H3K27ac enhancer. These data suggest that DES regulates gene expression in the neonatal mouse uterus by H3K27ac association at ERa binding sites near estrogen-regulated genes. Overall design: Mice were treated neonatally with DES (1 mg/kg) on days 1-5 and uteri collected on PND5, 4 hrs after the last treatment. Uteri were pooled (4-6 per sample). For H3K27me3 and H3K4me3 ChIP seq there is one sample deposited here. For H3K27ac and H3K4me1 ChIP seq there are two biological replicates for each condition.