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.