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

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.