Chromatin Interaction and Histone Mark Signatures Associated With TBXT Expression in Metastatic Lung Cancer

TY - JOUR

T1 - Chromatin Interaction and Histone Mark Signatures Associated With TBXT Expression in Metastatic Lung Cancer

AU - Yaa, Reuben M.

AU - Schilder, Brian M.

AU - Acemel, Rafael D.

AU - Wardle, Fiona C.

N1 - Publisher Copyright: © 2025 The Author(s). Genes, Chromosomes and Cancer published by Wiley Periodicals LLC.

PY - 2025/3/31

Y1 - 2025/3/31

N2 - 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.

AB - 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.

KW - 4C-seq

KW - A549

KW - cells

KW - ChIP-seq

KW - epigenomics

KW - H358

KW - H460

KW - lung cancer

KW - TBXT

UR - https://www.scopus.com/pages/publications/105000702706

U2 - 10.1002/gcc.70041

DO - 10.1002/gcc.70041

M3 - Article

C2 - 40099944

AN - SCOPUS:105000702706

SN - 1045-2257

VL - 64

JO - Genes Chromosomes and Cancer

JF - Genes Chromosomes and Cancer

IS - 3

M1 - e70041

ER -