Volume 12 Supplement 1

17th International Conference on Human Retroviruses: HTLV and Related Viruses

Open Access

HTLV-1 inserts an ectopic CTCF-binding site into the human genome

  • Yorifumi Satou1, 2, 3Email author,
  • Miyazato Paola2, 3,
  • Ko Ishihara2,
  • Asami Fukuda2, 3,
  • Kisato Nosaka2,
  • Takehisa Watanabe2,
  • Aileen Rowan1,
  • Mitsuyoshi Nakao2 and
  • Charles RM Bangham1
Retrovirology201512(Suppl 1):P12

https://doi.org/10.1186/1742-4690-12-S1-P12

Published: 28 August 2015

HTLV-1 genes are encoded on both strands of the provirus, such as tax in the plus and HBZ in the minus strand. The HBZ gene is constitutively expressed from the negative strand of the integrated provirus, whereas plus-strand expression, required for viral propagation to uninfected cells, is expressed only intermittently in vivo, perhaps to escape from host immune surveillance. However, it remains unknown what regulates this pattern of proviral transcription in vivo. We have found that CTCF binds to the HTLV-1 provirus. CTCF is a DNA-binding protein that plays a fundamental role in controlling higher-order chromatin structure and gene expression in vertebrates. We identified several candidate regions for CTCF binding in the HTLV-1 genome. Chromatin immunoprecipitation assays showed that CTCF bound selectively to the pX region of HTLV-1. Furthermore, electromobility shift assays revealed that CTCF bound directly to the pX DNA sequence. Consistent with the CTCF binding, there was a sharp border of histone modification patterns at the pX region, consistent with CTCF's role as a chromatin insulator. Finally, the CTCF-binding region (1bp) showed enhancer-blocking activity. The CTCF binding and epigenetic border were detectable not only in HTLV-1 cell lines and ATL cell lines but also in fresh PBMCs of ATL patients. These observations suggest that CTCF plays a central role in the regulation of HTLV-1 transcription.

#Poster award winnder - 1st place

Authors’ Affiliations

(1)
Department of Immunology, Imperial College London
(2)
Kumamoto University
(3)
International Research Center for Medical Sciences (IRCMS), Kumamoto University

Copyright

© Satou et al. 2015

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/4.0), 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.

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