Chromatin interaction and histone mark signatures associated with TBXT expression in metastatic lung cancer
Author(s)
Yaa, Reuben M
Schilder, Brian M
Acemel, Rafael D
Wardle, Fiona C
Type
Journal Article
Abstract
Background
TBXT, a member of the T-box transcription factor family, drives epithelial-to-mesenchymal transition in the metastasis of some cancers. However, the relationship between the epigenetic regulatory landscape and its expression in lung cancers remains elusive.
Methods
Circularized chromosome capture combined with sequencing (4C-seq) was employed to analyze physical chromatin interactions at the TBXT loci in the lung cancer cell line H460, a high TBXT-expressing cell line, compared to H358 and A549, which do not express TBXT. To define the regulatory landscape, the targeted TBXT chromatin interactions were integrated with histone modification profiles from respective cells, followed with motif analysis.
Results
Our analysis identified distinct patterns of potential cis-regulatory elements (pCREs) associated with the TBXT promoter, with increased near-cis pCRE enrichment in the TBXT-expressing cells. Integration of pCREs with epigenetic histone modification revealed two unique pCREs in TBXT-expressing H460 cells enriched with the active histone mark H3K27ac, harboring binding sites for transcription factors of the forkhead box, zinc finger, and musculoaponeurotic fibrosarcoma families that are linked to cancer metastasis.
Conclusion
Our findings shed light on active chromatin interactions with TBXT expression in lung cancers, pointing to specific DNA elements and regulatory proteins that may be involved. This knowledge paves the way for understanding TBXT expression dynamics at the onset and progression of metastatic cancers.
TBXT, a member of the T-box transcription factor family, drives epithelial-to-mesenchymal transition in the metastasis of some cancers. However, the relationship between the epigenetic regulatory landscape and its expression in lung cancers remains elusive.
Methods
Circularized chromosome capture combined with sequencing (4C-seq) was employed to analyze physical chromatin interactions at the TBXT loci in the lung cancer cell line H460, a high TBXT-expressing cell line, compared to H358 and A549, which do not express TBXT. To define the regulatory landscape, the targeted TBXT chromatin interactions were integrated with histone modification profiles from respective cells, followed with motif analysis.
Results
Our analysis identified distinct patterns of potential cis-regulatory elements (pCREs) associated with the TBXT promoter, with increased near-cis pCRE enrichment in the TBXT-expressing cells. Integration of pCREs with epigenetic histone modification revealed two unique pCREs in TBXT-expressing H460 cells enriched with the active histone mark H3K27ac, harboring binding sites for transcription factors of the forkhead box, zinc finger, and musculoaponeurotic fibrosarcoma families that are linked to cancer metastasis.
Conclusion
Our findings shed light on active chromatin interactions with TBXT expression in lung cancers, pointing to specific DNA elements and regulatory proteins that may be involved. This knowledge paves the way for understanding TBXT expression dynamics at the onset and progression of metastatic cancers.
Date Issued
2025-03-01
Date Acceptance
2025-03-03
Citation
Genes, Chromosomes and Cancer, 2025, 64 (3)
ISSN
1045-2257
Publisher
Wiley
Journal / Book Title
Genes, Chromosomes and Cancer
Volume
64
Issue
3
Copyright Statement
© 2025 The Author(s). Genes, Chromosomes and Cancer published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40099944
Subjects
TBXT
4C‐seq
A549
ChIP‐seq
H358
H460
cells
epigenomics
lung cancer
Humans
Lung Neoplasms
Chromatin
Histone Code
Gene Expression Regulation, Neoplastic
Neoplasm Metastasis
Histones
Cell Line, Tumor
Promoter Regions, Genetic
Epigenesis, Genetic
Publication Status
Published
Coverage Spatial
United States
Article Number
e70041
Date Publish Online
2025-03-18