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

Stefanie J. Otto, Sean R. McCorkle, John Hover, Cecilia Conaco, Jong Jin Han, Soren Impey, Gregory S. Yochum, John J. Dunn, Richard H. Goodman, Gail Mandel

Research output: Contribution to journalArticle

170 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6729-6739
Number of pages11
JournalJournal of Neuroscience
Volume27
Issue number25
DOIs
StatePublished - Jun 20 2007

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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    Otto, S. J., McCorkle, S. R., Hover, J., Conaco, C., Han, J. J., Impey, S., Yochum, G. S., Dunn, J. J., Goodman, R. H., & Mandel, G. (2007). A new binding motif for the transcriptional repressor REST uncovers large gene networks devoted to neuronal functions. Journal of Neuroscience, 27(25), 6729-6739. https://doi.org/10.1523/JNEUROSCI.0091-07.2007