Brief Communication abstract
Nature Chemical Biology 4, 408 - 410 (2008)
Published online: 15 June 2008 | doi:10.1038/nchembio.95
Small-molecule activation of neuronal cell fate
Jay W Schneider1, Zhengliang Gao2, Shijie Li3, Midhat Farooqi3, Tie-Shan Tang4, Ilya Bezprozvanny4, Doug E Frantz5 & Jenny Hsieh2
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 Ca2+ influx. Ca2+-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.
- Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
- Department of Molecular Biology and Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
- Department of Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
- Department of Physiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
- Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
Correspondence to: Jenny Hsieh2 e-mail: jenny.hsieh@utsouthwestern.edu
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Small-molecule activation of neuronal cell fateNature Chemical Biology Brief Communication (01 Jul 2008)
