RNA sequencing for transcriptome comparison between HTLV-1 Tax(-) and Tax(+) cells in Adult T-cell leukemia cell lines (MT-1 and KK-1)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE108601 | GEO | 2018/02/02
REPOSITORIES: GEO
Similar Datasets
Project description:Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma (ATL) and HTLV-1–associated myelopathy, and its viral transactivator Tax is central to disrupting host transcriptional control. 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. Functionally, Tax and IRF4 co-expression cooperatively restructured chromatin accessibility and induced aberrant gene expression programs. Moreover, ATL-associated IRF4 mutants (K59R, L70V, and S114N) partially reproduced Tax-driven chromatin remodeling and transcriptional reprogramming, suggesting that convergent mechanisms drive leukemogenesis. Collectively, these findings demonstrate that Tax exploits IRF4 to establish a novel regulatory mechanism. This interaction drives widespread epigenomic reprogramming in HTLV-1–infected T-cells. Overall, our study underscores the central role of Tax in IRF4 exploitation to induce infection-specific epigenomic changes, which offers novel insights into ATL pathogenesis and therapeutic strategies.
2026-03-31 | GSE316420 | GEO
Project description:Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma (ATL) and HTLV-1–associated myelopathy, and its viral transactivator Tax is central to disrupting host transcriptional control. 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. Functionally, Tax and IRF4 co-expression cooperatively restructured chromatin accessibility and induced aberrant gene expression programs. Moreover, ATL-associated IRF4 mutants (K59R, L70V, and S114N) partially reproduced Tax-driven chromatin remodeling and transcriptional reprogramming, suggesting that convergent mechanisms drive leukemogenesis. Collectively, these findings demonstrate that Tax exploits IRF4 to establish a novel regulatory mechanism. This interaction drives widespread epigenomic reprogramming in HTLV-1–infected T-cells. Overall, our study underscores the central role of Tax in IRF4 exploitation to induce infection-specific epigenomic changes, which offers novel insights into ATL pathogenesis and therapeutic strategies.
2026-03-31 | GSE316417 | GEO
Project description:Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma (ATL) and HTLV-1–associated myelopathy, and its viral transactivator Tax is central to disrupting host transcriptional control. 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. Functionally, Tax and IRF4 co-expression cooperatively restructured chromatin accessibility and induced aberrant gene expression programs. Moreover, ATL-associated IRF4 mutants (K59R, L70V, and S114N) partially reproduced Tax-driven chromatin remodeling and transcriptional reprogramming, suggesting that convergent mechanisms drive leukemogenesis. Collectively, these findings demonstrate that Tax exploits IRF4 to establish a novel regulatory mechanism. This interaction drives widespread epigenomic reprogramming in HTLV-1–infected T-cells. Overall, our study underscores the central role of Tax in IRF4 exploitation to induce infection-specific epigenomic changes, which offers novel insights into ATL pathogenesis and therapeutic strategies.
2026-03-31 | GSE316419 | GEO
Project description:Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma (ATL) and HTLV-1–associated myelopathy, and its viral transactivator Tax is central to disrupting host transcriptional control. 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. Functionally, Tax and IRF4 co-expression cooperatively restructured chromatin accessibility and induced aberrant gene expression programs. Moreover, ATL-associated IRF4 mutants (K59R, L70V, and S114N) partially reproduced Tax-driven chromatin remodeling and transcriptional reprogramming, suggesting that convergent mechanisms drive leukemogenesis. Collectively, these findings demonstrate that Tax exploits IRF4 to establish a novel regulatory mechanism. This interaction drives widespread epigenomic reprogramming in HTLV-1–infected T-cells. Overall, our study underscores the central role of Tax in IRF4 exploitation to induce infection-specific epigenomic changes, which offers novel insights into ATL pathogenesis and therapeutic strategies.
2026-03-31 | GSE316418 | GEO
Project description:Human T-cell leukemia virus type 1 (HTLV-1) is linked to the development of adult T-cell leukemia (ATL) and the neuroinflammatory disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 Tax oncoprotein regulates viral gene expression and the NF-kB pathway to promote the survival of HTLV-1 infected T cells. In thsi study, we utilize a kinome-wide shRNA screen to identify the tyrosine kinase KDR/VEGFR2 as an essential survival factor of HTLV-1-transformed T cells. Inhibition of KDR induces apoptosis of Tax expressing HTLV-1-transformed cell lines and CD4+ T cells from HAM/TSP patients. Phosphoproteomics analysis of HTLV-1 transformed cells treated with a KDR inhibitor revealed inhibition of the phosphorylation of multiple receptors/cell surface proteins, ubiquitin conjugating systems, proteases, phosphatases, apoptotic regulatory factors, adhesion/extracellular matrix proteins and viral proteins. This work suggests that HTLV-1 Tax has hijacked KDR kinase activity to promote Tax stability and the proliferation and survival of HTLV-1 infected cells.
2024-06-14 | PXD051981 | Pride
Project description:RNA sequencing for transcriptome comparison between HTLV-1 Tax(-) and Tax(+) cells in Adult T-cell leukemia cell lines (MT-1 and KK-1)
| PRJNA427802 | ENA
Project description:The Tesi system allows analysis of HTLV-1 Tax's impact on the transcriptome of a human CD4+ T-cell which is not derived from leukemia but directly from normal human lymphocytes. By comparing cells with and without Tax, one can specifically filter for celluar genes that are either activated or repressed in the presence of Tax. Keywords: cell type comparison, Tax
2008-02-14 | GSE10508 | GEO
Project description:Human T-lymphotropic virus type 1 (HTLV-1) is associated with the development of Adult T-cell Leukemia, an aggressive CD4+ T-cells malignancy. Here, we have developed a new procedure to infect humanized mice with proviruses displaying specific mutations, such as one leading to the loss of the PDZ domain-binding motif (PBM) of Tax. In order to specifically analyze the in vivo role of the PBM of Tax, a comparative study of infected hu-mice was performed. We used next-generation sequencing to perform genome-wide transcriptomic analysis of T-cells infected with wild-type HTLV-1 virus or with virus bearing a mutated form of Tax lacking the PBM. Our results suggest that Tax PBM might be involved in the regulation of genes implicated in proliferation, apoptosis and cytoskeleton organization.
2018-02-14 | GSE102220 | GEO
Project description:Chronic NF-kB activation in inflammation and cancer has long been linked to persistent activation of NF-kB–responsive gene promoters. However, NF-kB factors also massively bind to gene bodies. Here, we demonstrate that recruitment of the NF-kB factor RELA to intragenic regions regulates alternative splicing upon NF-kB activation by the viral oncogene Tax of HTLV-1. Integrative analyses of RNA splicing and chromatin occupancy, combined with chromatin tethering assays, demonstrate that DNA-bound RELA interacts with and recruits the splicing regulator DDX17, in an NF-kB activation–dependent manner. This leads to alternative splicing of target exons due to the RNA helicase activity of DDX17. Similar results were obtained upon Tax-independent NF-kB activation, indicating that Tax likely exacerbates a physiological process where RELA provides splice target specificity. Collectively, our results demonstrate a physical and direct involvement of NF-kB in alternative splicing regulation, which significantly revisits our knowledge of HTLV-1 pathogenesis and other NF-kB–related diseases.
2020-05-12 | GSE123752 | GEO
Project description:IL-15 is recognized as a promising candidate for tumor immunotherapy and has been described as both a promoter of cancer and a promoter of anti-cancer immunity. IL-15 was discovered in cells transformed by HTLV-1, the etiologic agent of adult T cell leukemia / lymphoma (ATL) and the human retrovirus that carries the Tax oncogene. We have developed the TAX-LUC mouse model of ATL in which Tax expression drives both malignant transformation and luciferase expression, enabling non-invasive imaging of tumorigenesis in real time. To identify the role of IL-15 in spontaneous development of lymphoma in vivo, an IL-15-/- TAX-LUC strain was developed and examined. The absence of IL-15 resulted in aggressive tumor growth and accelerated mortality and demonstrated that IL-15 was not required for Tax-mediated lymphoma but was essential for anti-tumor immunity. Further analysis revealed a unique transcriptional profile in tumor cells that arise in the absence of IL-15 that included a significant increase in the expression of IL-1α and IL-1α-regulated cytokines. Moreover, anti-IL-1α antibodies and an IL-1 receptor antagonist (Anakinra) were used to interrogate the potential of IL-1α targeted therapies in this model. Taken together, these findings identify IL-15 and IL-1α as therapeutic targets in lymphoma. We used microarrays to compare the gene expression profile of tumors in IL-15-/- TAX-LUC mice to IL-15+/+ TAX-LUC mice
2013-06-11 | GSE46072 | GEO