Fra-1 regulates its target genes via binding to remote enhancers without exerting major control on chromatin architecture in triple negative breast cancers
| Autor: | Hughes Parrinello, Tony Kaoma, Raphaël Romero, Laurent Brehelin, Damien J. Downes, Charles-Henri Lecellier, Marc Piechaczyk, Kazem Zibara, Amal Zine El Aabidine, Fabienne Bejjani, Jim R. Hughes, Muhammad Ahmad Maqbool, Mathias Boulanger, Claire Tolza, Laurent Vallar, Jean-Christophe Andrau, Sophie Lèbre, Isabelle Jariel-Encontre, Marine Rohmer |
|---|---|
| Přispěvatelé: | Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), The Weatherall Institute of Molecular Medicine, University of Oxford [Oxford], Méthodes et Algorithmes pour la Bioinformatique (MAB), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut Montpelliérain Alexander Grothendieck (IMAG), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génomique Fonctionnelle - Montpellier GenomiX (IGF MGX), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Luxembourg Institute of Health (LIH), Lebanese University [Beirut] (LU) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
AcademicSubjects/SCI00010
Triple Negative Breast Neoplasms Fos-Related Antigen-2 Biology Epigenesis Genetic Transcriptome 03 medical and health sciences 0302 clinical medicine Transcription (biology) Cell Line Tumor [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Genetics Humans p300-CBP Transcription Factors [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Nucleotide Motifs Enhancer Promoter Regions Genetic Gene Transcription factor 030304 developmental biology 0303 health sciences Binding Sites Gene regulation Chromatin and Epigenetics Promoter [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] Chromatin Cell biology Gene Expression Regulation Neoplastic Transcription Factor AP-1 Enhancer Elements Genetic 030220 oncology & carcinogenesis Candidate Disease Gene Proto-Oncogene Proteins c-fos |
| Zdroj: | Nucleic Acids Research Nucleic Acids Research, Oxford University Press, 2021, 49 (5), pp.2488-2508. ⟨10.1093/nar/gkab053⟩ |
| ISSN: | 0305-1048 1362-4962 |
| DOI: | 10.1093/nar/gkab053⟩ |
| Popis: | The ubiquitous family of dimeric transcription factors AP-1 is made up of Fos and Jun family proteins. It has long been thought to operate principally at gene promoters and how it controls transcription is still ill-understood. The Fos family protein Fra-1 is overexpressed in triple negative breast cancers (TNBCs) where it contributes to tumor aggressiveness. To address its transcriptional actions in TNBCs, we combined transcriptomics, ChIP-seqs, machine learning and NG Capture-C. Additionally, we studied its Fos family kin Fra-2 also expressed in TNBCs, albeit much less. Consistently with their pleiotropic effects, Fra-1 and Fra-2 up- and downregulate individually, together or redundantly many genes associated with a wide range of biological processes. Target gene regulation is principally due to binding of Fra-1 and Fra-2 at regulatory elements located distantly from cognate promoters where Fra-1 modulates the recruitment of the transcriptional co-regulator p300/CBP and where differences in AP-1 variant motif recognition can underlie preferential Fra-1- or Fra-2 bindings. Our work also shows no major role for Fra-1 in chromatin architecture control at target gene loci, but suggests collaboration between Fra-1-bound and -unbound enhancers within chromatin hubs sometimes including promoters for other Fra-1-regulated genes. Our work impacts our view of AP-1. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|