Chromatin interaction and histone mark signatures associated with TBXT expression in metastatic lung cancer
The role of TBXT in cancer formation and progression is well studied, as is its expression regulation during embryonic development, but how its expression is activated and maintained in lung cancers remains elusive. Circularized chromosome capture combined with sequencing (4C-seq) was employed to analyze physical chromatin interactions with the TBXT promoter in the lung cancer cell line H460, a high TBXT expressing cell line, compared to H358 and A549, which do not express TBXT. Our analysis identified distinct patterns of potential cis-regulatory elements (pCREs) associated with the TBXT promoter, with increased near-cis pCRE enrichment in TBXT-expressing cells. Integration of pCREs with epigenetic histone modification revealed TBXT expression-specific regulatory landscapes, suggesting a role for epigenetic mechanisms in TBXT control. Two unique pCREs in TBXT-expressing H460 cells enriched with active histone mark H3K27ac, harbored binding sites for transcription factors of the forkhead box, zinc finger, and musculoaponeurotic fibrosarcoma families that are linked to cancer metastasis. Our findings shed light on the intricate control of 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 and ultimately developing new therapeutic strategies. Overall design: To investigate this, we employed circularized chromosome capture combined with sequencing (4C-seq) to analyze physical chromatin interactions with the TBXT promoter in lung cancer cell line H460, a TBXT expressing cell line compared to H358 and A549, non-TBXT expressors