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Nat Chem Biol. 2008 Jul;4(7):408-10. doi: 10.1038/nchembio.95. Epub 2008 Jun 15.

Small-molecule activation of neuronal cell fate.

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  • 1Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.

Abstract

We probed an epigenetic regulatory path from small molecule to neuronal gene activation. Isoxazole small molecules triggered robust neuronal differentiation in adult neural stem cells, rapidly signaling to the neuronal genome via Ca(2+) influx. Ca(2+)-activated CaMK phosphorylated and mediated nuclear export of the MEF2 regulator HDAC5, thereby de-repressing neuronal genes. These results provide new tools to explore the epigenetic signaling circuitry specifying neuronal cell fate and new leads for neuro-regenerative drugs.

PMID:
18552832
[PubMed - indexed for MEDLINE]

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