Transcriptional repression by REST: recruitment of Sin3A and histone deacetylase to neuronal genes

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). Althoug h two independent domains of REST are known to confer repression, the mecha nisms of transcriptional repression by REST remain obscure. We provide mult iple lines of evidence that the N-terminal domain of REST represses transcr iption of the GluR2 and type II sodium-channel genes by recruiting the core pressor Sin3A and histone deacetylase (HDAC) to the promoter region in nonn euronal cells. These results identify a general mechanism for controlling t he neuronal expression pattern of a specific set of genes via the RE1 silen cer element.