Potential interactions between the TBX4-FGF10 and SHH-FOXF1 signaling during human lung development revealed using ChIP-seq.
Potential interactions between the TBX4-FGF10 and SHH-FOXF1 signaling during human lung development revealed using ChIP-seq.
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DOI：
10.1186/s12931-021-01617-y
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发表时间：
2021-01-21
影响因子：
5.8
通讯作者：
Stankiewicz P
中科院分区：
文献类型：
--
作者：
Karolak JA;Gambin T;Szafranski P;Stankiewicz P
涉及 SHH-FOXF1、TBX4-FGF10 和 TBX2 通路的上皮间质信号传导是早期肺器官发生过程中重要的转录网络。然而，该途径中不同基因和蛋白质之间的精确调控相互作用尚不完全清楚。为了鉴定 TBX2 和 TBX4 全基因组结合位点，我们在人胎肺成纤维细胞 IMR-90 中进行了染色质免疫沉淀，然后进行了新一代测序 (ChIP-seq)。我们分别鉴定了 14,322 个和 1,862 个 TBX2 和 TBX4 结合高度富集的位点，其中 43.95% 和 18.79% 位于基因启动子区域。基因本体、通路富集和 DNA 结合基序分析揭示了许多与肺分支相关的过度表达的线索和转录因子结合基序，可以通过 TBX2 和/或 TBX4 进行转录调节。此外，还发现 TBX2 和 TBX4 结合位点在 FOXF1 及其反义长非编码 RNA FENDRR 周围和内部富集，表明 TBX4-FGF10 级联可能直接与 SHH-FOXF1 信号传导相互作用。我们强调了 TBX2 和 TBX4 驱动的转录网络的复杂性，并表明形态发生过程中这种串扰的破坏可以在肺发育障碍的病因学中发挥重要作用。
The epithelial-mesenchymal signaling involving SHH-FOXF1, TBX4-FGF10, and TBX2 pathways is an essential transcriptional network operating during early lung organogenesis. However, precise regulatory interactions between different genes and proteins in this pathway are incompletely understood. To identify TBX2 and TBX4 genome-wide binding sites, we performed chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) in human fetal lung fibroblasts IMR-90. We identified 14,322 and 1,862 sites strongly-enriched for binding of TBX2 and TBX4, respectively, 43.95% and 18.79% of which are located in the gene promoter regions. Gene Ontology, pathway enrichment, and DNA binding motif analyses revealed a number of overrepresented cues and transcription factor binding motifs relevant for lung branching that can be transcriptionally regulated by TBX2 and/or TBX4. In addition, TBX2 and TBX4 binding sites were found enriched around and within FOXF1 and its antisense long noncoding RNA FENDRR, indicating that the TBX4-FGF10 cascade may directly interact with the SHH-FOXF1 signaling. We highlight the complexity of transcriptional network driven by TBX2 and TBX4 and show that disruption of this crosstalk during morphogenesis can play a substantial role in etiology of lung developmental disorders.
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影响因子：
14.9
作者：
Kamburov A;Stelzl U;Lehrach H;Herwig R
通讯作者：
Herwig R
影响因子：
14.9
作者：
The Gene Ontology Consortium
通讯作者：
The Gene Ontology Consortium
影响因子：
2.7
作者：
Fernandes-Silva H;Correia-Pinto J;Moura RS
通讯作者：
Moura RS
影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA
影响因子：
2.7
作者：
Caprioli A;Villasenor A;Wylie LA;Braitsch C;Marty-Santos L;Barry D;Karner CM;Fu S;Meadows SM;Carroll TJ;Cleaver O
通讯作者：
Cleaver O