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Regulation of miR-200c/141 expression by intergenic DNA-looping and transcriptional read-through

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 transcr...

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Autores principales: Batista, Luciana, Bourachot, Brigitte, Mateescu, Bogdan, Reyal, Fabien, Mechta-Grigoriou, Fatima
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4727242/
https://www.ncbi.nlm.nih.gov/pubmed/26725650
http://dx.doi.org/10.1038/ncomms9959
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author Batista, Luciana
Bourachot, Brigitte
Mateescu, Bogdan
Reyal, Fabien
Mechta-Grigoriou, Fatima
author_facet Batista, Luciana
Bourachot, Brigitte
Mateescu, Bogdan
Reyal, Fabien
Mechta-Grigoriou, Fatima
author_sort Batista, Luciana
collection PubMed
description 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.
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spelling pubmed-47272422017-07-21 Regulation of miR-200c/141 expression by intergenic DNA-looping and transcriptional read-through Batista, Luciana Bourachot, Brigitte Mateescu, Bogdan Reyal, Fabien Mechta-Grigoriou, Fatima Nat Commun Article 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. Nature Publishing Group 2016-01-04 /pmc/articles/PMC4727242/ /pubmed/26725650 http://dx.doi.org/10.1038/ncomms9959 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Batista, Luciana
Bourachot, Brigitte
Mateescu, Bogdan
Reyal, Fabien
Mechta-Grigoriou, Fatima
Regulation of miR-200c/141 expression by intergenic DNA-looping and transcriptional read-through
title Regulation of miR-200c/141 expression by intergenic DNA-looping and transcriptional read-through
title_full Regulation of miR-200c/141 expression by intergenic DNA-looping and transcriptional read-through
title_fullStr Regulation of miR-200c/141 expression by intergenic DNA-looping and transcriptional read-through
title_full_unstemmed Regulation of miR-200c/141 expression by intergenic DNA-looping and transcriptional read-through
title_short Regulation of miR-200c/141 expression by intergenic DNA-looping and transcriptional read-through
title_sort regulation of mir-200c/141 expression by intergenic dna-looping and transcriptional read-through
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4727242/
https://www.ncbi.nlm.nih.gov/pubmed/26725650
http://dx.doi.org/10.1038/ncomms9959
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