Cargando…

Potential interactions between the TBX4-FGF10 and SHH-FOXF1 signaling during human lung development revealed using ChIP-seq

BACKGROUND: 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 unders...

Descripción completa

Detalles Bibliográficos
Autores principales: Karolak, Justyna A., Gambin, Tomasz, Szafranski, Przemyslaw, Stankiewicz, Paweł
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818749/
https://www.ncbi.nlm.nih.gov/pubmed/33478486
http://dx.doi.org/10.1186/s12931-021-01617-y
_version_ 1783638904182669312
author Karolak, Justyna A.
Gambin, Tomasz
Szafranski, Przemyslaw
Stankiewicz, Paweł
author_facet Karolak, Justyna A.
Gambin, Tomasz
Szafranski, Przemyslaw
Stankiewicz, Paweł
author_sort Karolak, Justyna A.
collection PubMed
description BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
format Online
Article
Text
id pubmed-7818749
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-78187492021-01-22 Potential interactions between the TBX4-FGF10 and SHH-FOXF1 signaling during human lung development revealed using ChIP-seq Karolak, Justyna A. Gambin, Tomasz Szafranski, Przemyslaw Stankiewicz, Paweł Respir Res Research BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. BioMed Central 2021-01-21 2021 /pmc/articles/PMC7818749/ /pubmed/33478486 http://dx.doi.org/10.1186/s12931-021-01617-y Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.
spellingShingle Research
Karolak, Justyna A.
Gambin, Tomasz
Szafranski, Przemyslaw
Stankiewicz, Paweł
Potential interactions between the TBX4-FGF10 and SHH-FOXF1 signaling during human lung development revealed using ChIP-seq
title Potential interactions between the TBX4-FGF10 and SHH-FOXF1 signaling during human lung development revealed using ChIP-seq
title_full Potential interactions between the TBX4-FGF10 and SHH-FOXF1 signaling during human lung development revealed using ChIP-seq
title_fullStr Potential interactions between the TBX4-FGF10 and SHH-FOXF1 signaling during human lung development revealed using ChIP-seq
title_full_unstemmed Potential interactions between the TBX4-FGF10 and SHH-FOXF1 signaling during human lung development revealed using ChIP-seq
title_short Potential interactions between the TBX4-FGF10 and SHH-FOXF1 signaling during human lung development revealed using ChIP-seq
title_sort potential interactions between the tbx4-fgf10 and shh-foxf1 signaling during human lung development revealed using chip-seq
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818749/
https://www.ncbi.nlm.nih.gov/pubmed/33478486
http://dx.doi.org/10.1186/s12931-021-01617-y
work_keys_str_mv AT karolakjustynaa potentialinteractionsbetweenthetbx4fgf10andshhfoxf1signalingduringhumanlungdevelopmentrevealedusingchipseq
AT gambintomasz potentialinteractionsbetweenthetbx4fgf10andshhfoxf1signalingduringhumanlungdevelopmentrevealedusingchipseq
AT szafranskiprzemyslaw potentialinteractionsbetweenthetbx4fgf10andshhfoxf1signalingduringhumanlungdevelopmentrevealedusingchipseq
AT stankiewiczpaweł potentialinteractionsbetweenthetbx4fgf10andshhfoxf1signalingduringhumanlungdevelopmentrevealedusingchipseq