Transient ER binding and p300 redistribution support a physiological squelching model for immediate ER-repressed genes

Selective transcriptional activation and repression of genes throughout signaling cascades and development are poorly understood. Transcription factors (TF) orchestrate patterns and magnitude of transcriptional response, but TF action, or inaction, is highly dependent upon TF kinetics, distance from genes, chromatin architecture, and the local occupancy of other TFs. We integrated genomic transcription, chromosome looping, TF binding, and chromatin structure data to analyze the molecular cascade that results from estradiol-induced (E2) signaling in human MCF-7 breast cancer cells and addressed the context-specific nature of gene regulation. We analyzed kinetic ChIP-seq that profiled the master regulator of the E2-mediated response, estrogen receptor (ER), and found that transient ER binding sites are specifically associated with enhancers of repressed genes. Overall design: We performed replicate ChIP-seq experiments prior to estrogen treatment and 2min, 5min, 10min, 40min, and 160min after E2 treatment.