title: Regulation of miR-200c/141 expression by intergenic DNA-looping and transcriptional read-through.
abstract: The miR-200 family members have been implicated in stress responses and ovarian tumorigenesis. Here, we find that miR-200c/141 transcription is intimately linked to the transcription of the proximal upstream gene PTPN6 (SHP1) in all physiological conditions tested. PTPN6 and miR-200c/141 are transcriptionally co-regulated by two complementary mechanisms. First, a bypass of the regular PTPN6 polyadenylation signal allows the transcription of the downstream miR-200c/141. Second, the promoters of the PTPN6 and miR-200c/141 transcription units physically interact through a 3-dimensional DNA loop and exhibit similar epigenetic regulation. Our findings highlight that transcription of intergenic miRNAs is a novel outcome of transcriptional read-through and reveal a yet unexplored type of DNA loop associating two closely located promoters. These mechanisms have significant relevance in ovarian cancers and stress response, pathophysiological conditions in which miR-200c/141 exert key functions.
authors.affiliation: Stress and Cancer Laboratory, Equipe Labelisée LNCC, Institut Curie, PSL Research University, 26, rue d'Ulm, Paris 75248, France.|Inserm, U830, Paris F-75248, France.
authors.forename: Luciana
authors.initials: L
authors.lastname: Batista
authors.affiliation: Stress and Cancer Laboratory, Equipe Labelisée LNCC, Institut Curie, PSL Research University, 26, rue d'Ulm, Paris 75248, France.|Inserm, U830, Paris F-75248, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bourachot
authors.affiliation: Stress and Cancer Laboratory, Equipe Labelisée LNCC, Institut Curie, PSL Research University, 26, rue d'Ulm, Paris 75248, France.|Inserm, U830, Paris F-75248, France.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Mateescu
authors.affiliation: Residual Tumor and Response to Treatment Laboratory, Department of Translational Research, Institut Curie, 26, rue d'Ulm, Paris 75248, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Reyal
authors.affiliation: Stress and Cancer Laboratory, Equipe Labelisée LNCC, Institut Curie, PSL Research University, 26, rue d'Ulm, Paris 75248, France.|Inserm, U830, Paris F-75248, France.
authors.forename: Fatima
authors.initials: F
authors.lastname: Mechta-Grigoriou
mesh_terms: D000818:Animals; D002460:Cell Line; D021901:DNA, Intergenic / Q000378:metabolism*; D057890:Epigenomics; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D021901:DNA, Intergenic; C533895:MIRN141 microRNA, human; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; C543718:Mirn141 microRNA, mouse; C543719:Mirn200 microRNA, mouse; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; C509248:Ptpn6 protein, mouse