title: miR-137 forms a regulatory loop with nuclear receptor TLX and LSD1 in neural stem cells.
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.
authors: Department of Neurosciences, Center for Gene Expression and Drug Discovery, Beckman Research Institute of City of Hope, 1500 E. Duarte Rd, Duarte, California 91010, USA.
authors: GuoQiang
authors: G
authors: Sun
authors: Peng
authors: P
authors: Ye
authors: Kiyohito
authors: K
authors: Murai
authors: Ming-Fei
authors: MF
authors: Lang
authors: Shengxiu
authors: S
authors: Li
authors: Heying
authors: H
authors: Zhang
authors: Wendong
authors: W
authors: Li
authors: Chelsea
authors: C
authors: Fu
authors: Jason
authors: J
authors: Yin
authors: Allen
authors: A
authors: Wang
authors: Xiaoxiao
authors: X
authors: Ma
authors: Yanhong
authors: Y
authors: Shi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D018274:Electroporation; D005260:Female; D056466:Histone Demethylases; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism*; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*
chemical_list: C551799:MIRN137 microRNA, mouse; D035683:MicroRNAs; C490258:Nr2e1 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; D056466:Histone Demethylases; C504076:KDM1a protein, mouse; D010089:Oxidoreductases, N-Demethylating