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

Piper, Michael, Barry, Guy, Harvey, Tracey J., McLeay, Robert, Smith, Aaron G., Harris, Lachlan, Mason, Sharon, Stringer, Brett W., Day, Bryan W., Wray, Naomi R., Gronostajski, Richard M., Bailey, Timothy L., Boyd, Andrew W. and Richards, Linda J. (2014) NFIB-mediated repression of the epigenetic factor Ezh2 regulates cortical development. Journal of Neuroscience, 34 8: 2921-2930. doi:10.1523/JNEUROSCI.2319-13.2014

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Author Piper, Michael
Barry, Guy
Harvey, Tracey J.
McLeay, Robert
Smith, Aaron G.
Harris, Lachlan
Mason, Sharon
Stringer, Brett W.
Day, Bryan W.
Wray, Naomi R.
Gronostajski, Richard M.
Bailey, Timothy L.
Boyd, Andrew W.
Richards, Linda J.
Title NFIB-mediated repression of the epigenetic factor Ezh2 regulates cortical development
Formatted title
NFIB-mediated repression of the epigenetic factor Ezh2 regulates cortical development
Journal name Journal of Neuroscience   Check publisher's open access policy
ISSN 0270-6474
1529-2401
Publication date 2014-02-19
Year available 2014
Sub-type Article (original research)
DOI 10.1523/JNEUROSCI.2319-13.2014
Open Access Status File (Publisher version)
Volume 34
Issue 8
Start page 2921
End page 2930
Total pages 10
Place of publication Washington, DC, United States
Publisher Society for Neuroscience
Language eng
Abstract 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.
Formatted abstract
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.
Keyword Cortex
Ezh2
Hippocampus
Neural progenitor cell
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID APP1022308
DP0984643
C026429
HL080624
FT120100170
Institutional Status UQ

 
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