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MBC in Press, published online ahead of print September 29, 2005
Mol. Biol. Cell 10.1091/mbc.E05-07-0687

A more recent version of this article appeared on December 1, 2005
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Submitted on July 28, 2005
Revised on September 15, 2005
Accepted on September 20, 2005

Distinct Profiles of REST Interactions with Its Target Genes at Different Stages of Neuronal Development

Yuh-Man Sun,*{dagger} Deborah J. Greenway,{dagger}{ddagger} Rory Johnson,* Miyoko Street,* Nikolai D. Belyaev,* Jim Deuchars,{sect} Thomas Bee,* Sandra Wilde,* and Noel J. Buckley*{sect}

Schools of *Biochemistry and Microbiology, {sect}Biomedical Sciences, and {ddagger}Biology, University of Leeds, Leeds LS2 9JT, United Kingdom

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.

{dagger}These authors contributed equally to this work.

Address correspondence to: Yuh-Man Sun (y.sun{at}bmb.leeds.ac.uk)




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