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Publication : Direct transcriptional induction of Gadd45gamma by Ascl1 during neuronal differentiation.

First Author  Huang HS Year  2010
Journal  Mol Cell Neurosci Volume  44
Issue  3 Pages  282-96
PubMed ID  20382226 Mgi Jnum  J:164126
Mgi Id  MGI:4830792 Doi  10.1016/j.mcn.2010.03.014
Citation  Huang HS, et al. (2010) Direct transcriptional induction of Gadd45gamma by Ascl1 during neuronal differentiation. Mol Cell Neurosci 44(3):282-96
abstractText  The basic helix-loop-helix transcription factor Ascl1 plays a critical role in the intrinsic genetic program responsible for neuronal differentiation. Here, we describe a novel model system of P19 embryonic carcinoma cells with doxycycline-inducible expression of Ascl1. Microarray hybridization and real-time PCR showed that these cells demonstrated increased expression of many neuronal proteins in a time- and concentration-dependent manner. Interestingly, the gene encoding the cell cycle regulator Gadd45gamma was increased earliest and to the greatest extent following Ascl1 induction. Here, we provide the first evidence identifying Gadd45gamma as a direct transcriptional target of Ascl1. Transactivation and chromatin immunoprecipitation assays identified two E-box consensus sites within the Gadd45gamma promoter necessary for Ascl1 regulation, and demonstrated that Ascl1 is bound to this region within the Gadd45gamma promoter. Furthermore, we found that overexpression of Gadd45gamma itself is sufficient to initiate some aspects of neuronal differentiation independent of Ascl1.
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