Journal
JOURNAL OF NEUROSCIENCE
Volume 34, Issue 8, Pages 2921-2930Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2319-13.2014
Keywords
cortex; Ezh2; hippocampus; neural progenitor cell; Nfib
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Funding
- National Health and Medical Research Council (NHMRC) [APP1022308]
- Australian Research Council [DP0984643]
- Cancer Council Queensland
- New York State Stem Cell Science [C026429]
- National Institutes of Health [HL080624]
- NHMRC Principal Research Fellowship
- Australian Research Council Future Fellowships [FT120100170, FT0991360]
- Australian Research Council [DP0984643] Funding Source: Australian Research Council
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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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