Interaction of the repressor element 1-silencing transcription factor (REST) with target genes.

The repressor element 1-silencing transcription factor (REST) has been proposed to restrict expression of repressor element 1 (RE1) bearing genes to differentiated neurons by silencing their expression in non-neural tissue. Here, we have examined the interaction of REST with the M(4) muscarinic acetylcholine receptor gene. We show that REST binds to the RE1 of the M(4) gene in those cell lines and brain regions where the M(4) gene is expressed but not in those where the M(4) is not expressed. Furthermore, in cells that express M(4), the presence of REST represses but is insufficient to silence transcription of M(4). In non-neural cells REST is absent from the RE1 of the silent M(4) gene and perturbation of REST function fails to induce M(4) expression. We propose that REST acts to regulate expression levels of some RE1-bearing genes in neural cells, thereby playing an important role in defining neuronal activity.