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Nat Commun. 2016 Jan 4;7:8959. doi: 10.1038/ncomms9959.

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

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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.
Residual Tumor and Response to Treatment Laboratory, Department of Translational Research, Institut Curie, 26, rue d'Ulm, Paris 75248, France.


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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