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Vol. 16, Issue 12, 5630-5638, December 2005
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* School of Biochemistry and Microbiology, University of Leeds, Leeds LS2 9JT, United Kingdom;
School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom; and
School of Biology, University of Leeds, Leeds LS2 9JT, United Kingdom
Submitted July 28, 2005;
Revised September 15, 2005;
Accepted September 20, 2005
Monitoring Editor: Marianne Bronner-Fraser
Differentiation of pluripotent embryonic stem (ES) cells through multipotent neural stem (NS) cells into differentiated neurons is accompanied by wholesale changes in transcriptional programs. One factor that is present at all three stages and a key to neuronal differentiation is the RE1-silencing transcription factor (REST/NRSF). Here, we have used a novel chromatin immunoprecipitation-based cloning strategy (SACHI) to identify 89 REST target genes in ES cells, embryonic hippocampal NS cells and mature hippocampus. The gene products are involved in all aspects of neuronal function, especially neuronal differentiation, axonal growth, vesicular transport and release, and ionic conductance. Most target genes are silent or expressed at low levels in ES and NS cells, but are expressed at much higher levels in hippocampus. These data indicate that the REST regulon is specific to each developmental stage and support the notion that REST plays distinct roles in regulating gene expression in pluripotent ES cells, multipotent NS cells, and mature neurons.
Abbreviations used: RE1, repressor element 1; NRSE, neuron-restrictive silencer element; REST, repressor element 1 silencing transcription factor; NRSF, neuron-restrictive silencing factor; ES, embryonic stem cell; NS, neural stem cell; EMSA, electrophoretic mobility shift assay.
The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).
These authors contributed equally to this work.
Address correspondence to: Yuh-Man Sun (y.sun{at}bmb.leeds.ac.uk).
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 S. J. Otto, S. R. McCorkle, J. Hover, C. Conaco, J.-J. Han, S. Impey, G. S. Yochum, J. J. Dunn, R. H. Goodman, and G. Mandel A New Binding Motif for the Transcriptional Repressor REST Uncovers Large Gene Networks Devoted to Neuronal Functions J. Neurosci., June 20, 2007; 27(25): 6729 - 6739. [Abstract] [Full Text] [PDF]
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L. Ooi, N. D. Belyaev, K. Miyake, I. C. Wood, and N. J. Buckley BRG1 Chromatin Remodeling Activity Is Required for Efficient Chromatin Binding by Repressor Element 1-silencing Transcription Factor (REST) and Facilitates REST-mediated Repression J. Biol. Chem., December 22, 2006; 281(51): 38974 - 38980. [Abstract] [Full Text] [PDF]
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