GSE132510
Epigenetic remodelling of enhancers in response to estrogen deprivation and re-stimulation [ChIP-Seq]
Estrogen hormones are implicated in a majority of breast cancers and estrogen receptor alpha (ER) orchestrates a complex molecular circuitry that is not yet fully elucidated. Here we investigated genome-wide DNA methylation, histone acetylation and transcription after estradiol (E2) deprivation and re-stimulation to better characterise the ability of ER to coordinate gene regulation. We found that E2 deprivation mostly resulted in DNA hypermethylation and histone deacetylation in enhancers. Transcriptome analysis revealed that E2 deprivation leads to a global down-regulation in gene expression. Enrichment analysis of transcription factor (TF) binding and motif occurrence in the proximity of E2 deprivation-mediated differentially methylated and acetylated sites reinforces the importance of AP-1 and FOX proteins, Finally, most deprivation-dependent epigenetic changes were reversed following E2 re-stimulation. Overall design: Control MCF-7 HTB-22 breast cancer cells (CTR) were cultured continuously for 14 days in E2-containing medium, while E2-deprived cells (E2D) were cultured in the same conditions as CTR only lacking E2. The re-stimulated cells (ReSt) were E2-deprived for 4 days and re-stimulated for the 10 following. Each treatment (CTR, E2D and ReSt) and timepoint (d0, d4, d14) is available in triplicates. See publication for schematic design