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RE-1 silencing transcription factor (REST): a regulator of neuronal development and neuronal/endocrine function

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Abstract

RE-1 silencing transcription factor (REST) is a transcriptional repressor that has been proposed to function as a master negative regulator of neurogenesis, as REST target genes encode neuronal receptors, ion channels, neuropeptides and synaptic proteins. During neuronal differentiation, REST expression levels are reduced, allowing expression of selected REST target genes. The analysis of neural stem/progenitor cells that are either devoid of REST or overexpress REST revealed that REST is not the master regulator that is solely responsible for the acquisition of the neuronal fate. Rather, REST provides a regulatory hub that coordinately regulates multiple tiers of neuronal development in vitro. In addition, REST may play an important role for maintaining the integrity of adult neurons. REST confers oxidative stress resistance and is essential for maintaining neuronal viability. Furthermore, the concentration of REST has been reported to influence the pathogenic outcome by neuronal diseases, including stroke, epilepsy and Alzheimer’s disease. Experiments performed with PC12 pheochromocytoma cells indicate that REST may function as a key regulator of the neurosecretory phenotype. Moreover, transgenic mice overexpressing REST in pancreatic β-cells showed impaired insulin secretion leading to significantly reduced plasma insulin levels. Based on the fact that REST plays a prominent role in controlling stimulus-induced secretion in endocrine cells, we propose that REST may also be important for neurotransmitter release via regulation of genes that encode important proteins of the exocytotic machinery.

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Acknowledgements

We thank Libby Guethlein for critical reading of the manuscript. The research of the laboratory concerning the function of transcription factors in the nervous and endocrine system systems is supported by the University of Saarland.

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  1. Department of Medical Biochemistry and Molecular Biology, University of Saarland Medical Center, Building 44, 66421, Homburg, Germany

    Gerald Thiel, Myriam Ekici & Oliver G. Rössler

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  1. Gerald Thiel
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Correspondence to Gerald Thiel.

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Thiel, G., Ekici, M. & Rössler, O.G. RE-1 silencing transcription factor (REST): a regulator of neuronal development and neuronal/endocrine function. Cell Tissue Res 359, 99–109 (2015). https://doi.org/10.1007/s00441-014-1963-0

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