Rewired chromatin structure and epigenetic gene dysregulation during HTLV-1 infection to leukemogenesis.

in Cancer science by Jun Mizuike, Kako Suzuki, Shu Tosaka, Yuta Kuze, Seiichiro Kobayashi, Makoto Nakashima, Koji Jimbo, Yasuhito Nannya, Yutaka Suzuki, Kaoru Uchimaru, Makoto Yamagishi

TLDR

  • This study looked at the changes in the genes and chromatin structure of cells infected with HTLV-1, a virus that causes a disease called adult T-cell leukemia-lymphoma (ATL). The study used RNA-seq and ATAC-seq to analyze the cells and found that HTLV-1 Tax directly affects the host chromatin structure, leading to the development of fundamental epigenomic characteristics. The study also identified several Tax target genes, including the RASGRP3-ERK pathway, indicating an impact on signaling pathways. The study highlights the genome-wide variability in chromatin structural property as a novel feature of HTLV-1 infection and may contribute to pathogenic mechanisms. The study suggests that further research is needed to investigate the role of epigenomic aberrations in the development of ATL and to identify novel therapeutic targets.

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) broadly impacts host genes, affecting the infected cell population and inducing the development of a disease with a poor prognosis, adult T-cell leukemia-lymphoma (ATL). This study aimed to provide a comprehensive epigenomic characterization of the infected cell population and evaluated the transcriptome and chromatin structures of peripheral blood cells in HTLV-1-infected individuals using RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin sequencing (ATAC-seq). The infected cells showed significant changes in gene expression patterns from the polyclonal stage and before ATL onset while demonstrating similarities to tumor-forming ATL cells. These similarities were a result of large-scale open chromatin changes, supporting the independent early formation of epigenomic aberrations as an underlying mechanism for later clonal propagation. This study also demonstrated that HTLV-1 Tax directly affects the host chromatin structure, thereby developing fundamental epigenomic characteristics. Several Tax target genes, including the RASGRP3-ERK pathway, were recognized, indicating an impact on signaling pathways. This genome-wide variability in chromatin structural property is a novel feature of HTLV-1 infection and may contribute to pathogenic mechanisms. In addition, it has crucial implications for better understanding the impact of HTLV-1 on the host genome and identifying novel therapeutic targets.

Overview

  • The study aims to provide a comprehensive epigenomic characterization of the infected cell population in HTLV-1-infected individuals using RNA-seq and ATAC-seq. The study evaluates gene expression patterns and chromatin structures of peripheral blood cells in HTLV-1-infected individuals before and after ATL onset. The study demonstrates that HTLV-1 Tax directly affects the host chromatin structure, thereby developing fundamental epigenomic characteristics. The study also identifies several Tax target genes, including the RASGRP3-ERK pathway, indicating an impact on signaling pathways. The study highlights the genome-wide variability in chromatin structural property as a novel feature of HTLV-1 infection and may contribute to pathogenic mechanisms. The study aims to better understand the impact of HTLV-1 on the host genome and identify novel therapeutic targets.

Comparative Analysis & Findings

  • The study compares gene expression patterns and chromatin structures of peripheral blood cells in HTLV-1-infected individuals before and after ATL onset. The study demonstrates that HTLV-1 Tax directly affects the host chromatin structure, thereby developing fundamental epigenomic characteristics. The study also identifies several Tax target genes, including the RASGRP3-ERK pathway, indicating an impact on signaling pathways. The study highlights the genome-wide variability in chromatin structural property as a novel feature of HTLV-1 infection and may contribute to pathogenic mechanisms.

Implications and Future Directions

  • The study's findings have significant implications for better understanding the impact of HTLV-1 on the host genome and identifying novel therapeutic targets. The study identifies several Tax target genes, including the RASGRP3-ERK pathway, indicating an impact on signaling pathways. The study highlights the genome-wide variability in chromatin structural property as a novel feature of HTLV-1 infection and may contribute to pathogenic mechanisms. The study suggests that further research is needed to investigate the role of epigenomic aberrations in the development of ATL and to identify novel therapeutic targets. The study also suggests that further research is needed to investigate the role of Tax in the development of ATL and to identify novel therapeutic targets.
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