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Silencing of human T-cell leukemia virus type I gene transcription by epigenetic mechanisms
BACKGROUND: Human T-cell leukemia virus type I (HTLV-I) causes adult T-cell leukemia (ATL) after a long latent period. Among accessory genes encoded by HTLV-I, the tax gene is thought to play a central role in oncogenesis. However, Tax expression is disrupted by several mechanims including genetic c...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2005
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1289293/ https://www.ncbi.nlm.nih.gov/pubmed/16242045 http://dx.doi.org/10.1186/1742-4690-2-64 |
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author | Taniguchi, Yuko Nosaka, Kisato Yasunaga, Jun-ichirou Maeda, Michiyuki Mueller, Nancy Okayama, Akihiko Matsuoka, Masao |
author_facet | Taniguchi, Yuko Nosaka, Kisato Yasunaga, Jun-ichirou Maeda, Michiyuki Mueller, Nancy Okayama, Akihiko Matsuoka, Masao |
author_sort | Taniguchi, Yuko |
collection | PubMed |
description | BACKGROUND: Human T-cell leukemia virus type I (HTLV-I) causes adult T-cell leukemia (ATL) after a long latent period. Among accessory genes encoded by HTLV-I, the tax gene is thought to play a central role in oncogenesis. However, Tax expression is disrupted by several mechanims including genetic changes of the tax gene, deletion/hypermethylation of 5'-LTR. To clarify the role of epigenetic changes, we analyzed DNA methylation and histone modification in the whole HTLV-I provirus genome. RESULTS: The gag, pol and env genes of HTLV-I provirus were more methylated than pX region, whereas methylation of 5'-LTR was variable and 3'-LTR was not methylated at all. In ATL cell lines, complete DNA methylation of 5'-LTR was associated with transcriptional silencing of viral genes. HTLV-I provirus was more methylated in primary ATL cells than in carrier state, indicating the association with disease progression. In seroconvertors, DNA methylation was already observed in internal sequences of provirus just after seroconversion. Taken together, it is speculated that DNA methylation first occurs in the gag, pol and env regions and then extends in the 5' and 3' directions in vivo, and when 5'-LTR becomes methylated, viral transcription is silenced. Analysis of histone modification in the HTLV-I provirus showed that the methylated provirus was associated with hypoacetylation. However, the tax gene transcript could not be detected in fresh ATL cells regardless of hyperacetylated histone H3 in 5'-LTR. The transcription rapidly recovered after in vitro culture in such ATL cells. CONCLUSION: These results showed that epigenetic changes of provirus facilitated ATL cells to evade host immune system by suppressing viral gene transcription. In addition, this study shows the presence of another reversible mechanism that suppresses the tax gene transcription without DNA methylation and hypoacetylated histone. |
format | Text |
id | pubmed-1289293 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2005 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-12892932005-11-24 Silencing of human T-cell leukemia virus type I gene transcription by epigenetic mechanisms Taniguchi, Yuko Nosaka, Kisato Yasunaga, Jun-ichirou Maeda, Michiyuki Mueller, Nancy Okayama, Akihiko Matsuoka, Masao Retrovirology Research BACKGROUND: Human T-cell leukemia virus type I (HTLV-I) causes adult T-cell leukemia (ATL) after a long latent period. Among accessory genes encoded by HTLV-I, the tax gene is thought to play a central role in oncogenesis. However, Tax expression is disrupted by several mechanims including genetic changes of the tax gene, deletion/hypermethylation of 5'-LTR. To clarify the role of epigenetic changes, we analyzed DNA methylation and histone modification in the whole HTLV-I provirus genome. RESULTS: The gag, pol and env genes of HTLV-I provirus were more methylated than pX region, whereas methylation of 5'-LTR was variable and 3'-LTR was not methylated at all. In ATL cell lines, complete DNA methylation of 5'-LTR was associated with transcriptional silencing of viral genes. HTLV-I provirus was more methylated in primary ATL cells than in carrier state, indicating the association with disease progression. In seroconvertors, DNA methylation was already observed in internal sequences of provirus just after seroconversion. Taken together, it is speculated that DNA methylation first occurs in the gag, pol and env regions and then extends in the 5' and 3' directions in vivo, and when 5'-LTR becomes methylated, viral transcription is silenced. Analysis of histone modification in the HTLV-I provirus showed that the methylated provirus was associated with hypoacetylation. However, the tax gene transcript could not be detected in fresh ATL cells regardless of hyperacetylated histone H3 in 5'-LTR. The transcription rapidly recovered after in vitro culture in such ATL cells. CONCLUSION: These results showed that epigenetic changes of provirus facilitated ATL cells to evade host immune system by suppressing viral gene transcription. In addition, this study shows the presence of another reversible mechanism that suppresses the tax gene transcription without DNA methylation and hypoacetylated histone. BioMed Central 2005-10-22 /pmc/articles/PMC1289293/ /pubmed/16242045 http://dx.doi.org/10.1186/1742-4690-2-64 Text en Copyright © 2005 Taniguchi et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 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. |
spellingShingle | Research Taniguchi, Yuko Nosaka, Kisato Yasunaga, Jun-ichirou Maeda, Michiyuki Mueller, Nancy Okayama, Akihiko Matsuoka, Masao Silencing of human T-cell leukemia virus type I gene transcription by epigenetic mechanisms |
title | Silencing of human T-cell leukemia virus type I gene transcription by epigenetic mechanisms |
title_full | Silencing of human T-cell leukemia virus type I gene transcription by epigenetic mechanisms |
title_fullStr | Silencing of human T-cell leukemia virus type I gene transcription by epigenetic mechanisms |
title_full_unstemmed | Silencing of human T-cell leukemia virus type I gene transcription by epigenetic mechanisms |
title_short | Silencing of human T-cell leukemia virus type I gene transcription by epigenetic mechanisms |
title_sort | silencing of human t-cell leukemia virus type i gene transcription by epigenetic mechanisms |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1289293/ https://www.ncbi.nlm.nih.gov/pubmed/16242045 http://dx.doi.org/10.1186/1742-4690-2-64 |
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