Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

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

ABSTRACT: 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. Independent duplicate array series, using on one array pooled ChIP triplicates prepared from separate MDA::ER or MCF-7 cell cultures treated with estradiol for 50 minutes.

ORGANISM(S): Homo sapiens

SUBMITTER: RaphaM-CM-+l MM-CM-)tivier

PROVIDER: E-GEOD-32132 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Dynamic estrogen receptor interactomes control estrogen-responsive trefoil Factor (TFF) locus cell-specific activities.

Quintin Justine J Le Péron Christine C Palierne Gaëlle G Bizot Maud M Cunha Stéphanie S Sérandour Aurélien A AA Avner Stéphane S Henry Catherine C Percevault Frédéric F Belaud-Rotureau Marc-Antoine MA Huet Sébastien S Watrin Erwan E Eeckhoute Jérôme J Legagneux Vincent V Salbert Gilles G Métivier Raphaël R

Molecular and cellular biology 20140421 13

Estradiol signaling is ideally suited for analyzing the molecular and functional linkages between the different layers of information directing transcriptional regulations: the DNA sequence, chromatin modifications, and the spatial organization of the genome. Hence, the estrogen receptor (ER) can bind at a distance from its target genes and engages timely and spatially coordinated processes to regulate their expression. In the context of the coordinated regulation of colinear genes, identifying ...[more]

PMID: 24752895

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Project description:Cellular responses to signalling pathways are often highly dynamic, however most analyses of developmental signalling pathways focus on a single endpoint. We have analyzed the temporal changes in transcription following a short Notch activation treatment and related these to the recruitment of the Notch pathway transcription factor, CSL [Suppressor of Hairless, Su(H), in Drosophila], and to the state of RNA Polymerase II (Pol II) binding. A total of 154 genes showed significant differential expression over time and their expression profiles stratified into 14 clusters based on temporal and quantitative differences in their responses. These differences were partially reflected in the profiles of Pol II and Su(H) binding. However, neither could fully account for the different response profiles. Furthermore, the timing of the different responses was unaffected by more prolonged Notch activation. Instead our data suggest that regulatory relationships between genes that segregate into different response clusters can partially account for the stratification. Thus, feed-forward repression, where products of early responding Enhancer of split bHLH genes (E(spl)bHLH) inhibit expression of endogenous repressors, is one mechanism that explains the profile of genes that exhibit delayed up-regulation. E(spl)bHLH genes may therefore be responsible for co-ordinating the Notch response of a wide spectrum of other targets, explaining their critical functions in many developmental and disease contexts. DmD8 cells were collected at 7 time points (0M-bM-^@M-^Y, 10M-bM-^@M-^Y, 20M-bM-^@M-^Y, 30M-bM-^@M-^Y, 40M-bM-^@M-^Y, 60M-bM-^@M-^Y and 100M-bM-^@M-^Y) after a 5 minute Notch stimulation as 3 independent replicates. Immunoprecipitation was performed with Su(H) antibody and compared to the total input DNA. Samples from replicates #1 and #2 were labelled with Cy5, and replicate #3 was labelled with Cy3 as a dye-swap. For time point 10M-bM-^@M-^Y, only 2 biological replicates were obtained.

Dataset Information

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

Publications

Dynamic estrogen receptor interactomes control estrogen-responsive trefoil Factor (TFF) locus cell-specific activities.

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