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Publication : NFIB-mediated repression of the epigenetic factor Ezh2 regulates cortical development.

First Author  Piper M Year  2014
Journal  J Neurosci Volume  34
Issue  8 Pages  2921-30
PubMed ID  24553933 Mgi Jnum  J:206928
Mgi Id  MGI:5553377 Doi  10.1523/JNEUROSCI.2319-13.2014
Citation  Piper M, et al. (2014) NFIB-Mediated Repression of the Epigenetic Factor Ezh2 Regulates Cortical Development. J Neurosci 34(8):2921-30
abstractText  Epigenetic mechanisms are essential in regulating neural progenitor cell self-renewal, with the chromatin-modifying protein Enhancer of zeste homolog 2 (EZH2) emerging as a central player in promoting progenitor cell self-renewal during cortical development. Despite this, how Ezh2 is itself regulated remains unclear. Here, we demonstrate that the transcription factor nuclear factor IB (NFIB) plays a key role in this process. Nfib(-/-) mice exhibit an increased number of proliferative ventricular zone cells that express progenitor cell markers and upregulation of EZH2 expression within the neocortex and hippocampus. NFIB binds to the Ezh2 promoter and overexpression of NFIB represses Ezh2 transcription. Finally, key downstream targets of EZH2-mediated epigenetic repression are misregulated in Nfib(-/-) mice. Collectively, these results suggest that the downregulation of Ezh2 transcription by NFIB is an important component of the process of neural progenitor cell differentiation during cortical development.
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