NFIB-mediated Repression of the Epigenetic Factor Ezh2 Regulates Cortical Development

Overview

Journal J Neurosci

Specialty Neurology

Date 2014 Feb 21

PMID 24553933

Citations 39

Authors

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

Affiliations

Soon will be listed here.

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.

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