AP-1 signaling by Fra-1 directly regulates HMGA1 oncogene transcription in triple negative breast cancers
dc.contributor.author | Tolza, C | |
dc.contributor.author | Bejjani, F | |
dc.contributor.author | Evanno, E | |
dc.contributor.author | Mahfoud, S | |
dc.contributor.author | Moquet-Torcy, G | |
dc.contributor.author | Gostan, T | |
dc.contributor.author | Maqbool, MA | |
dc.contributor.author | Kirsh, O | |
dc.contributor.author | Piechaczyk, M | |
dc.contributor.author | Jariel-Encontre, I | |
dc.date.accessioned | 2019-09-11T09:09:12Z | |
dc.date.available | 2019-09-11T09:09:12Z | |
dc.date.issued | 2019 | en |
dc.identifier.citation | Tolza C, Bejjani F, Evanno E, Mahfoud S, Moquet-Torcy G, Gostan T, et al. AP-1 signaling by Fra-1 directly regulates HMGA1 oncogene transcription in triple negative breast cancers. Mol Cancer Res. 2019 Jul 12. | en |
dc.identifier.pmid | 31300541 | en |
dc.identifier.doi | 10.1158/1541-7786.MCR-19-0036 | en |
dc.identifier.uri | http://hdl.handle.net/10541/621987 | |
dc.description.abstract | The architectural chromatin protein HMGA1 and the transcription factor Fra-1 are both overexpressed in aggressive Triple Negative Breast Cancers (TNBCs), where they both favor epithelial-to-mesenchymal transition, invasion and metastasis. We therefore explored the possibility that Fra-1 might be involved in enhanced transcription of the HMGA1 gene in TNBCs by exploiting cancer transcriptome data sets and resorting to functional studies combining RNA interference, mRNA- and transcriptional run-on assays, chromatin immunoprecipitation and chromosome conformation capture approaches in TNBC model cell lines. Our bioinformatic analysis indicated that Fra-1 and HMGA1 expressions positively correlate in primary samples of TNBC patients. Our functional studies showed that Fra-1 regulates HMGA1 mRNA expression at the transcriptional level via binding to enhancer elements located in the last two introns of the gene. Although Fra-1 binding is required for p300/CBP recruitment at the enhancer domain, this recruitment did not appear essential for Fra-1-stimulated HMGA1 gene expression. Strikingly, Fra-1 binding is required for efficient recruitment of RNA Polymerase II at the HMGA1 promoter. This is permitted owing to chromatin interactions bringing about the intragenic Fra-1-binding enhancers and the gene promoter region. Fra-1 is, however, not instrumental for chromatin loop formation at the HMGA1 locus but rather exerts its transcriptional activity by exploiting chromatin interactions preexisting to its binding. Implications: We demonstrate that Fra-1 bound to an intragenic enhancer region is required for RNA Pol II recruitement at the HMGA1 promoter. Thereby, we provide novel insights into the mechanisms whereby Fra-1 exerts its pro-oncogenic transcriptional actions in the TNBC pathological context. | en |
dc.language.iso | en | en |
dc.relation.url | https://dx.doi.org/10.1158/1541-7786.MCR-19-0036 | en |
dc.title | AP-1 signaling by Fra-1 directly regulates HMGA1 oncogene transcription in triple negative breast cancers | en |
dc.type | Article | en |
dc.contributor.department | Institut de Genetique Moleculaire de Montpellier, CNRS, University of Montpellier | en |
dc.identifier.journal | Molecular Cancer Research | en |
dc.description.note | en] |