Cell-specific and spatio-temporal controls of the estrogen-responsive trefoil factor (TFF) locus activity.II

Cell-specific transcriptional regulations exerted by the estrogen (E2) receptor alpha (ER) heavily rely upon timely and spatially coordinated processes. We engaged a comparative analysis of such dynamic molecular events at the TFF locus harbouring a cluster of genes co-regulated by E2, in two distinct breast cancer cell lines. Using a combination of methods, we show that the recruitment of ER on cell-specific sites triggers dynamic local modifications of chromatin, which are coordinated in time all along the locus. DNA-FISH experiments further demonstrate that these changes are associated with an E2-dependent reduction in plasticity of this genomic region and are dependent upon cohesin. Importantly, 3C/4C experiments and the use of triplex forming oligonucleotides (TFOs) allowed us to precisely map the three-dimensional network of regulatory events that permits the estrogenic response of this genomic region. These data also evidenced an unexpected functional redundancy of enhancers. Samples (GSM587996-GSM588013): A 18 chip study aiming to characterize Estradiol (E2)-sensitive genes in MCF-7 and MDA::ER cells following 4h or 16h treatment with E2. RNAs were prepared from three independent triplicate experiments. Each of the three technical replicate correspond to pooled RNAs from 1 experiment. Controls for these experiments are 6 arrays corresponding to vehicle-treated MCF-7 and MDA::ER cells.