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Curr Opin Genet Dev. 2013 Oct;23(5):591-8. doi: 10.1016/j.gde.2013.07.001.

Reprogramming human fibroblasts to neurons by recapitulating an essential microRNA-chromatin switch.

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  • 1Howard Hughes Medical Institute, Department of Pathology and Developmental Biology, Stanford University Medical School, Stanford, CA 94305, USA.

Abstract

The development of the vertebrate nervous system requires a switch of ATP-dependent chromatin remodeling mechanisms, which occurs by substituting subunits within these complexes near cell cycle exit. This switching involves a triple negative genetic circuitry in which REST represses miR-9 and miR-124, which in turn repress BAF53a, which in turn repress the homologous neuron-specific BAF53b. Recapitulation of this microRNA/chromatin switch in human fibroblasts converts them to neurons. The genes involved in this fate-determining chromatin switch play genetically dominant roles in several human neurologic diseases suggesting that they are rate-limiting for aspects of human neural development. We review how this switch in ATP-dependent chromatin complexes might interface with traditional ideas about neural determination and reprogramming.

Copyright © 2013 Elsevier Ltd. All rights reserved.

PMID:
24035011
[PubMed - indexed for MEDLINE]
PMCID:
PMC3951511
Free PMC Article
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