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RESEARCH PAPER
1 Medical Research Council Laboratory for Molecular Cell Biology, Cell Biology Unit, and the Biology Department, University College London, London WC1E 6BT, United Kingdom; 2 Centre for Brain Repair, University of Cambridge, Cambridge CB2 2PY, United Kingdom
We showed previously that purified rat oligodendrocyte precursor cells (OPCs) can be induced by extracellular signals to convert to multipotent neural stem-like cells (NSLCs), which can then generate both neurons and glial cells. Because the conversion of precursor cells to stem-like cells is of both intellectual and practical interest, it is important to understand its molecular basis. We show here that the conversion of OPCs to NSLCs depends on the reactivation of the sox2 gene, which in turn depends on the recruitment of the tumor suppressor protein Brca1 and the chromatin-remodeling protein Brahma (Brm) to an enhancer in the sox2 promoter. Moreover, we show that the conversion is associated with the modification of Lys 4 and Lys 9 of histone H3 at the same enhancer. Our findings suggest that the conversion of OPCs to NSLCs depends on progressive chromatin remodeling, mediated in part by Brca1 and Brm.
[Keywords: Oligodendrocyte precursor cells; neural stem cells; Sox2; Brca1; Brm; histone modification]
Received May 17, 2004; revised version accepted September 21, 2004.
3 Corresponding author.
E-MAIL tk294{at}cam.ac.uk; FAX 44-1223-334121.
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