Record ID

WUTb3b404aa38f24fec878c0a78970d0fb0

Author

Justyna A. Karolak Justyna A. Karolak,, Undefined Affiliation

Tomasz Gambin Tomasz Gambin,, The Institute of Computer Science (FEIT/ICS)Faculty of Electronics and Information Technology (FEIT)

Przemyslaw Szafranski Przemyslaw Szafranski,, Author's external affiliation: Department of Molecular and Human Genetics

P. Stankiewicz P. Stankiewicz,, Undefined Affiliation

Journal series

Respiratory Research, ISSN 1465-993X, e-ISSN 1465-9921, [1465-9921]

Issue year

2021

Vol

22

No

1

Pages

1-15

ASJC Classification

2740 Pulmonary and Respiratory Medicine

Abstract in original language

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 bind-ing 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 disrup-tion of this crosstalk during morphogenesis can play a substantial role in etiology of lung developmental disorders.Keywords:Transcriptional regulation, Motif enrichment, Lung morphogenesis

DOI

DOI:10.1186/s12931-021-01617-y Opening in a new tab

URL

https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-021-01617-y Opening in a new tab

Language

eng (en) English

License

CC BY

Score (nominal)

100

Score source

journalList

Score

Ministerial score = 100.0, 19-06-2021, ArticleFromJournal

Publication indicators

GS Citations = 2.0; Scopus SNIP: 2017 = 1.154; WoS Impact Factor: 2018 (2 years)= 3.829 - 2018 (5 years)=4.184

Citation count

2

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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or PerishOpening in a new tab system.