The miR-141/200 familly of micro RNAs control oxidative stress and impact on ovarian tumorigenesis. Here the authors show that the transcription of miR-200c/141 is regulated through transcriptional read-through of the upstream gene PTPN6, and DNA looping linking the PTPN6 and miR-200c/141 promoters.

The miR-200 family members have been implicated in stress responses and ovarian tumorigenesis.

Researchers 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.

Authors 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.

http://www.nature.com/ncomms/2016/160104/ncomms9959/full/ncomms9959.html