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First published online November 2, 2006
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2006-0207v1
25/2/354    most recent
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Submitted on April 11, 2006
Accepted on October 19, 2006

Tissue-Specific Stem Cells

REST Maintains a Repressive Chromatin Environment in Embryonic Hippocampal Neural Stem Cells

Deborah J. Greenway 1, Miyoko Street 1, Aaron Jeffries 2, Noel J. Buckley 2*

1 Institute of Membrane and Systems Biology, University of Leeds, Leeds, United Kingdom
2 King's College London, Centre for the Cellular Basis of Behaviour, Institute of Psychiatry, London, United Kingdom

* To whom correspondence should be addressed. E-mail: noel.buckley{at}iop.kcl.ac.uk.


  Abstract

The control of gene expression in neural stem cells is key to understanding their developmental and therapeutic potential yet we know little of the transcriptional mechanisms that underlie their differentiation. Recent evidence has implicated the RE1 silencing transcription factor (REST), in neuronal differentiation. However the means by which REST regulates transcription in neural stem cells remain unclear. Here, we show that REST recruits distinct co-repressor platforms in neural stem cells. REST is able to both silence and repress neuronal genes in embryonic hippocampal neural stem cells by creating a chromatin environment that contains both repressive local epigenetic signature, characterized by low levels of histones H4 and H3K9 acetylation and elevated dimethylation of H3K9, in addition to H3K4 methylation, which are characteristic of gene activation. Further, inhibition of REST function leads to activation of several neuron-specific genes but does not lead to overt formation of mature neurons supporting the notion that REST regulates part, but not all, of the neuronal differentiation program.

Key Words. REST, chromatin, histones, neural stem cell, epigenetics, transcription




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