HTLV-1 Tax reshapes the DNA-binding pattern of transcription factor IRF4 and disrupts host gene regulation [ChIP-seq]

Although individual interactions between Tax and host factors have been investigated, their global network and functional impact remain unclear. In this study, we performed proteomic analyses of Tax-associated complexes in HTLV-1–infected T-cells and mapped interactions between host factors and Tax.

In addition to known nuclear factor kappa B (NF-κB) regulators, we identified the transcription factor interferon regulatory factor 4 (IRF4) as a novel interactor. Co-immunoprecipitation experiments confirmed Tax–IRF4 binding, and chromatin profiling revealed that Tax reprograms genome-wide IRF4 occupancy. In infected T-cells, IRF4 was enriched in super-enhancer (SE) regions, where Tax, IRF4, and NF-κB factors colocalized at ATL-related loci, and this was accompanied by histone acetylation changes and transcriptional activation.