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First published online November 2, 2006
Stem Cells Vol. 25 No. 2 February 2007, pp. 354 -363
doi:10.1634/stemcells.2006-0207; www.StemCells.com
© 2007 AlphaMed Press

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TISSUE-SPECIFIC STEM CELLS

RE1 Silencing Transcription Factor Maintains a Repressive Chromatin Environment in Embryonic Hippocampal Neural Stem Cells

Deborah J. Greenwaya, Miyoko Streeta, Aaron Jeffriesb, Noel J. Buckleyb

aInstitute of Membrane and Systems Biology, University of Leeds, Leeds, United Kingdom;
bKing's College London, Centre for the Cellular Basis of Behaviour, Institute of Psychiatry, London, United Kingdom

Key Words. RE1 silencing transcription factor • Chromatin • Histones • Neural stem cell • Epigenetics • Transcription

Correspondence: Noel J. Buckley, Ph.D., Centre for the Cellular Basis of Behaviour, The James Black Centre, King's College London, Institute of Psychiatry, 125 Coldharbour Lane, London, SE5 9NU, United Kingdom. Telephone: +44 (0)20 7848 0784; Fax: +44 (0)20 7848 5308; e-mail: noel.buckley{at}iop.kcl.ac.uk

Received April 11, 2006; accepted for publication October 19, 2006.
First published online in STEM CELLS EXPRESS   November 2, 2006.



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 corepressor 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) and H3K4 methylation, which are characteristic of gene activation. Furthermore, 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.




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M. Ekici, M. Hohl, F. Schuit, A. Martinez-Serrano, and G. Thiel
Transcription of Genes Encoding Synaptic Vesicle Proteins in Human Neural Stem Cells: CHROMATIN ACCESSIBILITY, HISTONE METHYLATION PATTERN, AND THE ESSENTIAL ROLE OF REST
J. Biol. Chem., April 4, 2008; 283(14): 9257 - 9268.
[Abstract] [Full Text] [PDF]


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