title: FOXA and master transcription factors recruit Mediator and Cohesin to the core transcriptional regulatory circuitry of cancer cells.
abstract: Controlling the transcriptional program is essential to maintain the identity and the biological functions of a cell. The Mediator and Cohesin complexes have been established as central cofactors controlling the transcriptional program in normal cells. However, the distribution, recruitment and importance of these complexes in cancer cells have not been fully investigated. Here we show that FOXA and master transcription factors are part of the core transcriptional regulatory circuitry of cancer cells and are essential to recruit M ediator and Cohesin. Indeed, Mediator and Cohesin occupied the enhancer and promoter regions of actively transcribed genes and maintained the proliferation and colony forming potential. Through integration of publically available ChIP-Seq datasets, we predicted the core transcriptional regulatory circuitry of each cancer cell. Unexpectedly, for all cells investigated, the pioneer transcription factors FOXA1 and/or FOXA2 were identified in addition to cell-specific master transcription factors. Loss of both types of transcription factors phenocopied the loss of Mediator and Cohesin. Lastly, the master and pioneer transcription factors were essential to recruit Mediator and Cohesin to regulatory regions of actively transcribed genes. Our study proposes that maintenance of the cancer cell state is dependent on recruitment of Mediator and Cohesin through FOXA and master transcription factors.
authors.affiliation: Centre de Recherche sur le Cancer de l'Université Laval, Québec, Canada.|Centre de recherche du CHU de Québec - Université Laval, Québec, Canada.
authors.forename: Michèle
authors.initials: M
authors.lastname: Fournier
authors.affiliation: Centre de Recherche sur le Cancer de l'Université Laval, Québec, Canada.|Centre de recherche du CHU de Québec - Université Laval, Québec, Canada.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Bourriquen
authors.affiliation: Centre de Recherche sur le Cancer de l'Université Laval, Québec, Canada.|Centre de recherche du CHU de Québec - Université Laval, Québec, Canada.
authors.forename: Fabien C
authors.initials: FC
authors.lastname: Lamaze
authors.affiliation: Centre de Recherche sur le Cancer de l'Université Laval, Québec, Canada.|Centre de recherche du CHU de Québec - Université Laval, Québec, Canada.
authors.forename: Maxime C
authors.initials: MC
authors.lastname: Côté
authors.affiliation: Centre de Recherche sur le Cancer de l'Université Laval, Québec, Canada.|Centre de recherche du CHU de Québec - Université Laval, Québec, Canada.
authors.forename: Éric
authors.initials: É
authors.lastname: Fournier
authors.affiliation: Centre de recherche du CHU de Québec - Université Laval, Québec, Canada.
authors.forename: Charles
authors.initials: C
authors.lastname: Joly-Beauparlant
authors.affiliation: Centre de Recherche sur le Cancer de l'Université Laval, Québec, Canada.|Centre de recherche du CHU de Québec - Université Laval, Québec, Canada.
authors.forename: Vicky
authors.initials: V
authors.lastname: Caron
authors.affiliation: Centre de recherche du CHU de Québec - Université Laval, Québec, Canada.|Département de médecine moléculaire, Faculté de Médecine, Université Laval, Québec, Canada.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Gobeil
authors.affiliation: Centre de recherche du CHU de Québec - Université Laval, Québec, Canada.|Département de médecine moléculaire, Faculté de Médecine, Université Laval, Québec, Canada.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Droit
authors.affiliation: Centre de Recherche sur le Cancer de l'Université Laval, Québec, Canada.|Centre de recherche du CHU de Québec - Université Laval, Québec, Canada.|Département de biologie moléculaire, biochimie médicale et pathologie, Faculté de Médecine, Université Laval, Québec, Canada.
authors.forename: Steve
authors.initials: S
authors.lastname: Bilodeau
mesh_terms: D000072283:A549 Cells; D018797:Cell Cycle Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D056892:Mediator Complex / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D025341:Principal Component Analysis; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D051541:Hepatocyte Nuclear Factor 3-alpha; D056892:Mediator Complex; D000097722:Cohesins; C496499:FOXA1 protein, human