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miR-137 forms a regulatory loop with nuclear receptor TLX and LSD1 in neural stem cells

Author

Listed:
  • GuoQiang Sun

    (Center for Gene Expression and Drug Discovery, Cancer Center, Beckman Research Institute of City of Hope)

  • Peng Ye

    (Center for Gene Expression and Drug Discovery, Cancer Center, Beckman Research Institute of City of Hope)

  • Kiyohito Murai

    (Center for Gene Expression and Drug Discovery, Cancer Center, Beckman Research Institute of City of Hope)

  • Ming-Fei Lang

    (Center for Gene Expression and Drug Discovery, Cancer Center, Beckman Research Institute of City of Hope)

  • Shengxiu Li

    (Center for Gene Expression and Drug Discovery, Cancer Center, Beckman Research Institute of City of Hope)

  • Heying Zhang

    (Center for Gene Expression and Drug Discovery, Cancer Center, Beckman Research Institute of City of Hope)

  • Wendong Li

    (Center for Gene Expression and Drug Discovery, Cancer Center, Beckman Research Institute of City of Hope)

  • Chelsea Fu

    (Center for Gene Expression and Drug Discovery, Cancer Center, Beckman Research Institute of City of Hope)

  • Jason Yin

    (Center for Gene Expression and Drug Discovery, Cancer Center, Beckman Research Institute of City of Hope)

  • Allen Wang

    (Center for Gene Expression and Drug Discovery, Cancer Center, Beckman Research Institute of City of Hope)

  • Xiaoxiao Ma

    (Center for Gene Expression and Drug Discovery, Cancer Center, Beckman Research Institute of City of Hope)

  • Yanhong Shi

    (Center for Gene Expression and Drug Discovery, Cancer Center, Beckman Research Institute of City of Hope)

Abstract

miR-137 is a brain-enriched microRNA. Its role in neural development remains unknown. Here we show that miR-137 has an essential role in controlling embryonic neural stem cell fate determination. miR-137 negatively regulates cell proliferation and accelerates neural differentiation of embryonic neural stem cells. In addition, we show that the histone lysine-specific demethylase 1 (LSD1), a transcriptional co-repressor of nuclear receptor TLX, is a downstream target of miR-137. In utero electroporation of miR-137 in embryonic mouse brains led to premature differentiation and outward migration of the transfected cells. Introducing a LSD1 expression vector lacking the miR-137 recognition site rescued miR-137-induced precocious differentiation. Furthermore, we demonstrate that TLX, an essential regulator of neural stem cell self-renewal, represses the expression of miR-137 by recruiting LSD1 to the genomic regions of miR-137. Thus, miR-137 forms a feedback regulatory loop with TLX and LSD1 to control the dynamics between neural stem cell proliferation and differentiation during neural development.

Suggested Citation

  • GuoQiang Sun & Peng Ye & Kiyohito Murai & Ming-Fei Lang & Shengxiu Li & Heying Zhang & Wendong Li & Chelsea Fu & Jason Yin & Allen Wang & Xiaoxiao Ma & Yanhong Shi, 2011. "miR-137 forms a regulatory loop with nuclear receptor TLX and LSD1 in neural stem cells," Nature Communications, Nature, vol. 2(1), pages 1-10, September.
    • Handle: RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1532
    DOI: 10.1038/ncomms1532
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