4.8 Article

A noncoding RNA regulates the neurogenin1 gene locus during mouse neocortical development

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NATL ACAD SCIENCES
DOI: 10.1073/pnas.1202956109

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  1. Core Research for Evolutional Science and Technology (CREST) of the Japan Science and Technology Agency
  2. Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan
  3. MEXT of Japan
  4. JSPS
  5. Global COE Program (Integrative Life Science Based on the Study of Biosignaling Mechanisms), MEXT, Japan
  6. Grants-in-Aid for Scientific Research [23249015] Funding Source: KAKEN

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The proneural basic helix-loop-helix (bHLH) transcription factor neurogenin1 (Neurog1) plays a pivotal role in neuronal differentiation during mammalian development. The spatiotemporal control of the Neurog1 gene expression is mediated by several specific enhancer elements, although how these elements regulate the Neurog1 locus has remained largely unclear. Recently it has been shown that a large number of enhancer elements are transcribed, but the regulation and function of the resulting transcripts have been investigated for only several such elements. We now show that an enhancer element located 5.8-7.0 kb upstream of the mouse Neurog1 locus is transcribed. The production of this transcript, designated utNgn1, is highly correlated with that of Neurog1 mRNA during neuronal differentiation. Moreover, knockdown of utNgn1 by a corresponding short interfering RNA inhibits the production of Neurog1 mRNA in response to induction of neuronal differentiation. We also found that production of utNgn1 is suppressed by polycomb group (PcG) proteins, which inhibit the expression of Neurog1. Our results thus suggest that a noncoding RNA transcribed from an enhancer element positively regulates transcription at the Neurog1 locus.

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