title: NFIB-mediated repression of the epigenetic factor Ezh2 regulates cortical development.
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.
authors.affiliation: Queensland Brain Institute, Institute for Molecular Bioscience, and The School of Biomedical Sciences, The University of Queensland, Brisbane, Australia 4069, QIMR Berghofer Medical Research Institute, Brisbane, Australia 4029, and Department of Biochemistry, Program in Genetics, Genomics and Bioinformatics, Center of Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo, Buffalo, New York 14203.
authors.forename: Michael
authors.initials: M
authors.lastname: Piper
authors.forename: Guy
authors.initials: G
authors.lastname: Barry
authors.forename: Tracey J
authors.initials: TJ
authors.lastname: Harvey
authors.forename: Robert
authors.initials: R
authors.lastname: McLeay
authors.forename: Aaron G
authors.initials: AG
authors.lastname: Smith
authors.forename: Lachlan
authors.initials: L
authors.lastname: Harris
authors.forename: Sharon
authors.initials: S
authors.lastname: Mason
authors.forename: Brett W
authors.initials: BW
authors.lastname: Stringer
authors.forename: Bryan W
authors.initials: BW
authors.lastname: Day
authors.forename: Naomi R
authors.initials: NR
authors.lastname: Wray
authors.forename: Richard M
authors.initials: RM
authors.lastname: Gronostajski
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Bailey
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Boyd
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Richards
mesh_terms: D000818:Animals; D002452:Cell Count; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development* / Q000502:physiology; D024202:Electrophoretic Mobility Shift Assay; D000071221:Enhancer of Zeste Homolog 2 Protein; D044127:Epigenesis, Genetic / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D046228:Microarray Analysis; D009154:Mutation / Q000235:genetics / Q000502:physiology; D051839:NFI Transcription Factors / Q000235:genetics* / Q000502:physiology*; D058953:Neural Stem Cells / Q000502:physiology; D063151:Polycomb Repressive Complex 2 / Q000235:genetics* / Q000502:physiology*; D061251:Primary Cell Culture; D011401:Promoter Regions, Genetic / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D051839:NFI Transcription Factors; C484683:Nfib protein, mouse; D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; D063151:Polycomb Repressive Complex 2
keywords: Ezh2; Nfib; cortex; hippocampus; neural progenitor cell