Epigenomic enhancer annotation reveals a key role for NFIX in neural stem cell quiescence

Martynoga, Ben, Mateo, Juan L., Zhou, Bo, Andersen, Jimena, Achimastou, Angeliki, Urbán, Noelia, van den Berg, Debbie, Georgopoulou, Dimitra, Hadjur, Suzana, Wittbrodt, Joachim, Ettwiller, Laurence, Piper, Michael, Gronostajski, Richard M. and Guillemot, Francois (2013) Epigenomic enhancer annotation reveals a key role for NFIX in neural stem cell quiescence. Genes and Development, 27 16: 1769-1786. doi:10.1101/gad.216804.113

Author Martynoga, Ben
Mateo, Juan L.
Zhou, Bo
Andersen, Jimena
Achimastou, Angeliki
Urbán, Noelia
van den Berg, Debbie
Georgopoulou, Dimitra
Hadjur, Suzana
Wittbrodt, Joachim
Ettwiller, Laurence
Piper, Michael
Gronostajski, Richard M.
Guillemot, Francois
Title Epigenomic enhancer annotation reveals a key role for NFIX in neural stem cell quiescence
Journal name Genes and Development   Check publisher's open access policy
ISSN 0890-9369
Publication date 2013-08-15
Sub-type Article (original research)
DOI 10.1101/gad.216804.113
Open Access Status DOI
Volume 27
Issue 16
Start page 1769
End page 1786
Total pages 18
Place of publication Woodbury, NY, United States
Publisher Cold Spring Harbor Laboratory Press
Collection year 2014
Language eng
Formatted abstract
The majority of neural stem cells (NSCs) in the adult brain are quiescent, and this fraction increases with aging. Although signaling pathways that promote NSC quiescence have been identified, the transcriptional mechanisms involved are mostly unknown, largely due to lack of a cell culture model. In this study, we first demonstrate that NSC cultures (NS cells) exposed to BMP4 acquire cellular and transcriptional characteristics of quiescent cells. We then use epigenomic profiling to identify enhancers associated with the quiescent NS cell state. Motif enrichment analysis of these enhancers predicts a major role for the nuclear factor one (NFI) family in the gene regulatory network controlling NS cell quiescence. Interestingly, we found that the family member NFIX is robustly induced when NS cells enter quiescence. Using genome-wide location analysis and overexpression and silencing experiments, we demonstrate that NFIX has a major role in the induction of quiescence in cultured NSCs. Transcript profiling of NS cells overexpressing or silenced for Nfix and the phenotypic analysis of the hippocampus of Nfix mutant mice suggest that NFIX controls the quiescent state by regulating the interactions of NSCs with their microenvironment.
Keyword Epigenetics
Neural stem cells
Nuclear factor one
Transcription factor
Genome-wide maps
Adult hippocampus
Chromatin state
Progenitor proliferation
Histone modifications
Differentiated cells
Expression analysis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2014 Collection
School of Biomedical Sciences Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 27 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 27 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 15 Sep 2013, 00:12:55 EST by System User on behalf of School of Biomedical Sciences