The transcriptional repressor REST is a critical regulator of the neurosecretory phenotype.

作者: Alexander W. Bruce , Alena Krejčí , Lezanne Ooi , James Deuchars , Ian C. Wood

DOI: 10.1111/J.1471-4159.2006.04010.X

关键词:

摘要: Release of distinct cellular cargoes in response to specific stimuli is a process fundamental all higher eukaryotes and controlled by the regulated secretory pathway (RSP). However, mechanism which genes involved RSP are selectively expressed, leading establishment appropriate functioning secretion remaining largely unknown. Using rat pheochromocytoma cell line PC12, we provide evidence that, controlling expression many RSP, transcriptional repressor REST can regulate this hence neurosecretory phenotype. Introduction transgenes into PC12 cells leads repression genes, products secretion. Moreover, chromatin immunoprecipitation assays show that repressed recruit recombinant protein RE1 sites within their promoters abrogation function reactivation these transcripts. In addition observed effects, expressing have fewer granules reduction ability store release noradrenaline. Furthermore, an important trigger for synaptic release, influx calcium through voltage-operated channels, compromised. This first demonstration transcription factor directly controls major components provides further insight REST.

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