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

GuoQiang Sun, Peng Ye, Kiyohito Murai, Ming-Fei Lang, Shengxiu Li, Heying Zhang, Wendong Li, Chelsea Fu, Jason Yin, Allen Wang, Xiaoxiao Ma and Yanhong Shi ()
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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

Nature Communications, 2011, vol. 2, issue 1, 1-10

Abstract: 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.

Date: 2011
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DOI: 10.1038/ncomms1532

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