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

Author

Listed:
  • Luciana Batista

    (Stress and Cancer Laboratory, Equipe Labelisée LNCC, Institut Curie, PSL Research University
    Inserm, U830)

  • Brigitte Bourachot

    (Stress and Cancer Laboratory, Equipe Labelisée LNCC, Institut Curie, PSL Research University
    Inserm, U830)

  • Bogdan Mateescu

    (Stress and Cancer Laboratory, Equipe Labelisée LNCC, Institut Curie, PSL Research University
    Inserm, U830)

  • Fabien Reyal

    (Residual Tumor and Response to Treatment Laboratory, Institut Curie)

  • Fatima Mechta-Grigoriou

    (Stress and Cancer Laboratory, Equipe Labelisée LNCC, Institut Curie, PSL Research University
    Inserm, U830)

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.

Suggested Citation

  • Luciana Batista & Brigitte Bourachot & Bogdan Mateescu & Fabien Reyal & Fatima Mechta-Grigoriou, 2016. "Regulation of miR-200c/141 expression by intergenic DNA-looping and transcriptional read-through," Nature Communications, Nature, vol. 7(1), pages 1-17, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms9959
    DOI: 10.1038/ncomms9959
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    Cited by:

    1. Monika Licaj & Rana Mhaidly & Yann Kieffer & Hugo Croizer & Claire Bonneau & Arnaud Meng & Lounes Djerroudi & Kevin Mujangi-Ebeka & Hocine R. Hocine & Brigitte Bourachot & Ilaria Magagna & Renaud Lecl, 2024. "Residual ANTXR1+ myofibroblasts after chemotherapy inhibit anti-tumor immunity via YAP1 signaling pathway," Nature Communications, Nature, vol. 15(1), pages 1-27, December.

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