A Single Zinc Finger Motif in the Silencing Factor Rest Represses the Neural-Specific Type II Sodium Channel Promoter.

Abstract

The type II voltage-dependent sodium chan- nel is present in neuronal cells, where it mediates the prop- agationofnerveimpulses.RestrictedexpressionofthetypeII sodium channel gene to neurons is due, at least in part, to binding of the repressor protein REST (also termed NRSF or XBR) to the RE1 (also called NRSE) sequence in the type II sodium channel gene. Previous studies have shown that a domain in REST containing eight GL1-Kru ̈ppel zinc finger motifs mediates DNA binding. Deletional and GAL4-fusion geneanalysesnowrevealrepressordomainsthatlieoutsideof the DNA-binding domain in both the amino and carboxyl termini of REST. Mutational analysis further identifies a single zinc finger motif in the carboxyl-terminal domain as beingessentialforrepressingtypeIIsodiumchannelreporter genes. These studies reveal two domains in REST that may mediate interactions with other proteins involved in restrict- ingexpressionofalargesetofgenestothevertebratenervous system.