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 Goodman, Gail Mandel

Research output: Contribution to journalArticle

164 Citations (Scopus)

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

Fingerprint

Gene Regulatory Networks
Transcriptional Silencer Elements
Genes
Nerve Tissue
Neuroendocrine Tumors
Gene Silencing
Chromatin
RE1-silencing transcription factor
Carcinogenesis
Proteins
Transcription Factors
Genome
Phenotype
Kidney
Neurons
Cell Line

Keywords

  • Binding motif
  • Neuroendocrine tumors
  • REST
  • Serial analysis of chromatin occupancy
  • Synaptic transmission
  • Transcription

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

A new binding motif for the transcriptional repressor REST uncovers large gene networks devoted to neuronal functions. / Otto, Stefanie J.; McCorkle, Sean R.; Hover, John; Conaco, Cecilia; Han, Jong Jin; Impey, Soren; Yochum, Gregory S.; Dunn, John J.; Goodman, Richard; Mandel, Gail.

In: Journal of Neuroscience, Vol. 27, No. 25, 20.06.2007, p. 6729-6739.

Research output: Contribution to journalArticle

Otto, Stefanie J. ; McCorkle, Sean R. ; Hover, John ; Conaco, Cecilia ; Han, Jong Jin ; Impey, Soren ; Yochum, Gregory S. ; Dunn, John J. ; Goodman, Richard ; Mandel, Gail. / A new binding motif for the transcriptional repressor REST uncovers large gene networks devoted to neuronal functions. In: Journal of Neuroscience. 2007 ; Vol. 27, No. 25. pp. 6729-6739.
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