A new binding motif for the transcriptional repressor REST uncovers large gene networks devoted to neuronal functions

The repressor element 1 ( RE1) silencing transcription factor ( REST) helps preserve the identity of nervous tissue by silencing neuronal genes in non- neural tissues. Moreover, in an epithelial model of tumorigenesis, loss of REST function is associated with loss of adhesion, suggesting the aberrant expression of REST- controlled genes encoding this property. To date, no adhesion molecules under REST control have been identified. Here, we used serial analysis of chromatin occupancy to perform genome- wide identification of REST- occupied target sequences ( RE1 sites) in a kidney cell line. We discovered novel REST- binding motifs and found that the number of RE1 sites far exceeded previous estimates. A large family of targets encoding adhesion proteins was identified, as were genes encoding signature proteins of neuroendocrine tumors. Unexpectedly, genes considered exclusively non- neuronal also contained an RE1 motif and were expressed in neurons. This supports the model that REST binding is a critical determinant of neuronal phenotype.