An overlapping set of genes is regulated by both NFIB and the glucocorticoid receptor during lung maturation.
An overlapping set of genes is regulated by both NFIB and the glucocorticoid receptor during lung maturation.
复制标题
DOI：
10.1186/1471-2164-15-231
复制
发表时间：
2014-03-25
期刊：
影响因子：
4.4
通讯作者：
Bailey TL
中科院分区：
文献类型：
--
作者：
Lajoie M;Hsu YC;Gronostajski RM;Bailey TL
肺成熟是小鼠和人类的晚期胎儿发育事件。因此，肺部不成熟是早产儿的一个严重问题。糖皮质激素受体 (Nr3c1) 或 NFIB 转录因子基因的破坏会因肺不成熟而导致围产期死亡。在这两种基因敲除中，表型包括细胞过度增殖、囊化失败和上皮分化标志物表达减少。这种相似性表明这两个基因可能共同调节肺成熟所必需的一组特定基因。我们使用 NFIB 的 ChIP-seq 数据以及两者的 RNA 表达数据和基序分析分析了这两种转录因子在调节转录中的作用。我们关于肺中 NFIB E16.5 的新 ChIP-seq 数据显示 NFIB 与 NFI 基序结合。该基序在 Nfib-KO 小鼠 E18.5 表达不足的基因启动子中过度表达，表明 NFIB 具有激活剂作用。利用来自 Nr3c1-KO 小鼠的可用微阵列数据，我们进一步鉴定了在 Nfib 和 Nr3c1 敲除中表达不足的 52 个基因，重叠程度比偶然预期的重叠程度大 13.1 倍。最后，我们在这些推定靶基因的启动子中寻找最近发表的 738 个转录因子基序的富集，发现 NFIB 和糖皮质激素受体基序是最富集的，这表明这些基因的一个子集可能被 Nfib 和 Nr3c1 直接激活。我们的数据为 Nfib 和 Nr3c1 共同调节与肺成熟相关的基因提供了第一个证据。他们还证实 NFIB 的体内 DNA 结合特异性与之前在体外观察到的相同，并且与其他 NFI 家族成员 NFIA、NFIC 和 NFIX 高度相似。
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. 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. 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.
登录
查看更多内容
DOI：
10.1093/bioinformatics/btr064
发表时间：
2011-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Grant CE;Bailey TL;Noble WS
通讯作者：
Noble WS
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
2.7
作者：
Hsu YC;Osinski J;Campbell CE;Litwack ED;Wang D;Liu S;Bachurski CJ;Gronostajski RM
通讯作者：
Gronostajski RM
影响因子：
5.5
作者：
Bird, Anthony D.;Tan, Kheng H.;Cole, Timothy J.
通讯作者：
Cole, Timothy J.
影响因子：
16
作者：
Capdevila, J;Tsukui, T;Belmonte, JCI
通讯作者：
Belmonte, JCI