Transcriptional regulation of neuronal differentiation: the epigenetic layer of complexity - PubMed (original) (raw)

Review

Transcriptional regulation of neuronal differentiation: the epigenetic layer of complexity

Mary E Hamby et al. Biochim Biophys Acta. 2008 Aug.

Abstract

The transcriptional programs of neural progenitor cells change dynamically during neurogenesis, a process regulated by both intrinsic and extrinsic factors. Although many of the transcription factors required for neuronal differentiation have long been identified, we are only at the brink of understanding how epigenetic mechanisms influence transcriptional activity and the accessibility of transcription factors to bind consensus cis-elements. Herein, we delineate the chief epigenetic modifications and the machinery responsible for these alterations. Further, we review the epigenetic modifications presently known to participate in the maintenance of the neural progenitor cell state and in the regulation of neuronal differentiation.

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Figures

Fig. 1

Key events in the NPC to neuron transition. During neurogenesis, many events in the cell are orchestrated to ensure proper neuronal differentiation. Although there are a number of players, miR-124 expression and the downregulation of REST play key roles in globally decreasing expression of non-neuronal genes while simultaneously enhancing neuron-specific gene expression. When REST expression is downregulated, this enables the derepression of numerous pro-neuronal genes allowing for pro-neural bHLHs to instigate the further induction of neuronal genes. Moreover, dismissal of REST from the RE1 sites on miR-124 eradicates the silencing effect that REST has on miR-124 [57], allowing for induction of miR-124 expression. Once miR-124 is induced, it can then degrade its numerous non-neuronal targets [57,76]. Collectively, the downregulation of REST and upregulation of miRNA provide a swift transition from NPC to neuron.

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Transcriptional regulation of neuronal differentiation: the epigenetic layer of complexity - PubMed (original) (raw)