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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-01-04

AUTHORS

Luciana Batista, Brigitte Bourachot, Bogdan Mateescu, Fabien Reyal, Fatima Mechta-Grigoriou

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. More... »

PAGES

8959

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncomms9959

DOI

http://dx.doi.org/10.1038/ncomms9959

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1027412191

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26725650


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