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

Abstract

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.

Long Noncoding RNAs Usher In a New Era in the Biology of Enhancers

“…For example, experiments analyzing developmental regulation of neurogenin1, a critical transcription factor required for brain development, revealed the presence of distal regulatory elements expressing long noncoding RNAs (Onoguchi et al, 2012). Functional depletion of these long noncoding RNAs, termed utNgn1, demonstrated their requirement for transcriptional activation of neurogenin 1 during development (Onoguchi et al, 2012).…”

Long non-coding RNA-dependent transcriptional regulation in neuronal development and disease

“…Importantly, both of these lncRNAs overlap sequences of ultra conserved elements implicated in neuronal development (Amaral et al, 2009; Onoguchi et al, 2012). UtNgn1 is required for Neurogenin1 ( Neurog1 ) transcription and PRC2-mediated repressive signals at the utNgn1 locus are associated with both decreases in utNgn1 and Neurog1 transcript abundance (Onoguchi et al, 2012).…”

Enhancer RNAs: the new molecules of transcription

“…Recent studies have started to shed some light on the biological relevance of eRNAs. An enhancer-like RNA was shown to regulate neurogenin 1 expression during mouse cortical development [31]. The eRNA expressed from the CE element upstream of the MYOD1 locus was shown to regulate the MyoD expression during the differentiation of C2C12 cells, underscoring the importance of eRNAs in myogenic gene expression programs [30].…”