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Published on: January 12, 2015
A noncoding RNA regulates the neurogenin1 gene locus during mouse neocortical development
Masahiro Onoguchi1, Yusuke Hirabayashi, Haruhiko Koseki
1Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113-0032, Japan.
Summary
A novel noncoding RNA, utNgn1, transcribed from a Neurog1 gene enhancer, promotes neuronal differentiation. This enhancer RNA is regulated by Polycomb group proteins and is essential for Neurog1 mRNA production.
Area of Science:
- Developmental Biology
- Gene Regulation
- Neuroscience
Background:
- Neurogenin1 (Neurog1) is a key transcription factor for neuronal differentiation.
- Enhancer elements regulate gene expression, but their transcribed products are often uncharacterized.
- The precise mechanisms controlling Neurog1 locus regulation remain incompletely understood.
Purpose of the Study:
- To investigate the role of transcribed enhancer elements in Neurog1 gene regulation.
- To characterize a novel transcript from a Neurog1 upstream enhancer.
- To determine the functional significance of this enhancer transcript in neuronal differentiation.
Main Methods:
- Identification and characterization of a transcribed enhancer element upstream of the mouse Neurog1 locus.
- Correlation analysis of utNgn1 and Neurog1 mRNA levels during neuronal differentiation.
- Short interfering RNA (siRNA) knockdown of utNgn1.
- Investigation of Polycomb group (PcG) protein regulation of utNgn1.
Main Results:
- A novel transcript, utNgn1, was identified from an enhancer 5.8-7.0 kb upstream of the Neurog1 locus.
- utNgn1 production strongly correlated with Neurog1 mRNA during neuronal differentiation.
- Knockdown of utNgn1 impaired Neurog1 mRNA production upon differentiation induction.
- Polycomb group proteins were found to suppress utNgn1 production.
Conclusions:
- The noncoding RNA utNgn1 positively regulates transcription at the Neurog1 locus.
- utNgn1 plays a crucial role in mediating Neurog1 expression during neuronal differentiation.
- Enhancer RNAs represent a significant layer of gene regulation in mammalian development.
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