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

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...

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Autores principales: Lajoie, Mathieu, Hsu, Yu-Chih, Gronostajski, Richard M, Bailey, Timothy L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4023408/
https://www.ncbi.nlm.nih.gov/pubmed/24661679
http://dx.doi.org/10.1186/1471-2164-15-231
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author Lajoie, Mathieu
Hsu, Yu-Chih
Gronostajski, Richard M
Bailey, Timothy L
author_facet Lajoie, Mathieu
Hsu, Yu-Chih
Gronostajski, Richard M
Bailey, Timothy L
author_sort Lajoie, Mathieu
collection PubMed
description 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.
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spelling pubmed-40234082014-05-16 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 Bailey, Timothy L BMC Genomics Research Article 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. BioMed Central 2014-03-25 /pmc/articles/PMC4023408/ /pubmed/24661679 http://dx.doi.org/10.1186/1471-2164-15-231 Text en Copyright © 2014 Lajoie et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Lajoie, Mathieu
Hsu, Yu-Chih
Gronostajski, Richard M
Bailey, Timothy L
An overlapping set of genes is regulated by both NFIB and the glucocorticoid receptor during lung maturation
title An overlapping set of genes is regulated by both NFIB and the glucocorticoid receptor during lung maturation
title_full An overlapping set of genes is regulated by both NFIB and the glucocorticoid receptor during lung maturation
title_fullStr An overlapping set of genes is regulated by both NFIB and the glucocorticoid receptor during lung maturation
title_full_unstemmed An overlapping set of genes is regulated by both NFIB and the glucocorticoid receptor during lung maturation
title_short An overlapping set of genes is regulated by both NFIB and the glucocorticoid receptor during lung maturation
title_sort overlapping set of genes is regulated by both nfib and the glucocorticoid receptor during lung maturation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4023408/
https://www.ncbi.nlm.nih.gov/pubmed/24661679
http://dx.doi.org/10.1186/1471-2164-15-231
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