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

Michael Piper, Guy Barry, Tracey J. Harvey, Robert McLeay, Aaron G. Smith, Lachlan Harris, Sharon Mason, Brett W. Stringer, Bryan W. Day, Naomi R. Wray, Richard M. Gronostajski, Timothy L. Bailey, Andrew W. Boyd, Linda J. Richards

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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.

Original languageEnglish
Pages (from-to)2921-2930
Number of pages10
JournalJournal of Neuroscience
Volume34
Issue number8
DOIs
Publication statusPublished - 19 Feb 2014
Externally publishedYes

Keywords

  • Cortex
  • Ezh2
  • Hippocampus
  • Neural progenitor cell
  • Nfib

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    Piper, M., Barry, G., Harvey, T. J., McLeay, R., Smith, A. G., Harris, L., Mason, S., Stringer, B. W., Day, B. W., Wray, N. R., Gronostajski, R. M., Bailey, T. L., Boyd, A. W., & Richards, L. J. (2014). NFIB-mediated repression of the epigenetic factor Ezh2 regulates cortical development. Journal of Neuroscience, 34(8), 2921-2930. https://doi.org/10.1523/JNEUROSCI.2319-13.2014