Abstract
Many genes whose expression is restricted to neurons in the brain contain a silencer element (RE1/NRSE) that limits transcription in nonneuronal cells by binding the transcription factor REST (also named NRSF or XBR). Although two independent domains of REST are known to confer repression, the mechanisms of transcriptional repression by REST remain obscure. We provide multiple lines of evidence that the N-terminal domain of REST represses transcription of the GluR2 and type II sodium-channel genes by recruiting the corepressor Sin3A and histone deacetylase (HDAC) to the promoter region in nonneuronal cells. These results identify a general mechanism for controlling the neuronal expression pattern of a specific set of genes via the RE1 silencer element.
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Acknowledgements
We thank Rick Kahn for the mouse anti-myc antibody, David Anderson for the mouse anti-REST antibody, Stuart Schrieber for the HDAC constructs, Gerald Thiel for the myc-REST and Gal4-REST constructs, Gail Mandel for the type II sodium-channel promoter and Nancy F. Ciliax for neuronal cultures. We thank Jerry Boss, John Lucchesi and Steve Warren for comments on an early version of the manuscript. Supported by NIH grant NS36604 (R.D.) and an NRSA (S.J.M.).
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Huang, Y., Myers, S. & Dingledine, R. Transcriptional repression by REST: recruitment of Sin3A and histone deacetylase to neuronal genes. Nat Neurosci 2, 867–872 (1999). https://doi.org/10.1038/13165
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DOI: https://doi.org/10.1038/13165
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