An overlapping set of genes is regulated by both NFIB and the glucocorticoid receptor during lung maturation

Lajoie, Mathieu, Hsu, Yu-Chih, Gronostajski, Richard M. and Bailey, Timothy L. (2014) An overlapping set of genes is regulated by both NFIB and the glucocorticoid receptor during lung maturation. BMC Genomics, 15 1: . doi:10.1186/1471-2164-15-231

Author Lajoie, Mathieu
Hsu, Yu-Chih
Gronostajski, Richard M.
Bailey, Timothy L.
Title An overlapping set of genes is regulated by both NFIB and the glucocorticoid receptor during lung maturation
Journal name BMC Genomics   Check publisher's open access policy
ISSN 1471-2164
Publication date 2014-03-25
Year available 2014
Sub-type Article (original research)
DOI 10.1186/1471-2164-15-231
Open Access Status DOI
Volume 15
Issue 1
Total pages 13
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Formatted abstract
Background: Lung maturation is a late fetal developmental event in both mice and humans. Because of this, lung immaturity is a serious problem in premature infants. Disruption of genes for either the glucocorticoid receptor (Nr3c1) or the NFIB transcription factors results in perinatal lethality due to lung immaturity. In both knockouts, the phenotype includes excess cell proliferation, failure of saccularization and reduced expression of markers of epithelial differentiation. This similarity suggests that the two genes may co-regulate a specific set of genes essential for lung maturation.
Results: We analyzed the roles of these two transcription factors in regulating transcription using ChIP-seq data for NFIB, and RNA expression data and motif analysis for both. Our new ChIP-seq data for NFIB in lung at E16.5 shows that NFIB binds to a NFI motif. This motif is over-represented in the promoters of genes that are under-expressed in Nfib-KO mice at E18.5, suggesting an activator role for NFIB. Using available microarray data from Nr3c1-KO mice, we further identified 52 genes that are under-expressed in both Nfib and Nr3c1 knockouts, an overlap which is 13.1 times larger than what would be expected by chance. Finally, we looked for enrichment of 738 recently published transcription factor motifs in the promoters of these putative target genes and found that the NFIB and glucocorticoid receptor motifs were among the most enriched, suggesting that a subset of these genes may be directly activated by Nfib and Nr3c1.
Conclusions: Our data provide the first evidence for Nfib and Nr3c1 co-regulating genes related to lung maturation. They also establish that the in vivo DNA-binding specificity of NFIB is the same as previously seen in vitro, and highly similar to that of the other NFI-family members NFIA, NFIC and NFIX.
Keyword ChIP-seq analysis
Expression analysis
Glucocorticoid receptor
Lung development
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article # 231

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
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