- Poster presentation
- Open Access
HTLV-1 Tax disrupts the host epigenome by interacting with a Polycomb group protein EZH2
© Fujikawa et al; licensee BioMed Central Ltd. 2014
- Published: 7 January 2014
- H3K27 Methylation
- Histone H3K27
- H3K27 Trimethylation
- Polycomb Group Protein
- Epigenetic Abnormality
ATL is a highly aggressive T-cell neoplasm caused by HTLV-1. We have recently demonstrated that EZH2, a catalytic enzyme of histone H3K27 methylation, is overexpressed in ATL cells, which contributes to persistent NF-κB activation by repressing a tumor-suppressive miRNA, miR-31. This suggests that epigenetic abnormalities are closely associated with the molecular hallmarks of leukemic cells. However, the mechanisms by which epigenetic disruption is caused and sustained in HTLV-1 infected cells remain to be clarified. In the present study, we first found that Tax directly interacts with EZH2 in HTLV-1 infected cells. Given that epigenetic state is directly affected by cell lineage-dependent transcription factors and genetic background, we assessed the functional interconnection between HTLV-1 Tax and the histone methyltransferases in an appropriate model. Using a lentivirus vector, we introduced tax gene into peripheral blood mononuclear cells (PBMCs) and CD4+ T-cells from healthy donors and established Tax-transduced T-cells. In this model, we observed overexpression of EZH2, aberrant accumulation of H3K27 trimethylation, and epigenetic silencing of p21 cip1/waf1 , all of which have been observed in primary ATL cells. In addition, EZH2 inhibition reduced the viability of Tax-transduced T-cells. Our results strongly suggest that Tax epigenetically affects gene expression through its interaction with EZH2, and that Tax-dependent epigenetic abnormalities may be involved in determining the molecular characteristics of HTLV-1-infected cells as well as ATL cells. Since epigenetic marks are potentially reversible, development of genuine epigenetic-targeted drugs will hold great promise in treatment of HTLV-1-related diseases.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.