Identification of long-range chromatin interactions between HTLV-1 and the host genome
- Hiroko Yaguchi†1Email author,
- Anat Melamed†1,
- Aileen Rowan1,
- Lucy Cook1,
- Yorifumi Satou1, 2 and
- Charles R M Bangham1
© Yaguchi et al. 2015
Published: 28 August 2015
Human T-lymphotropic virus type I (HTLV-1) integration is known to be weakly biased towards genomically active regions but can occur throughout the genome. We have shown that there are of the order of 10^4 HTLV-1-infected T-cell clones in each individual, each clone defined by a unique genomic integration site of the single-copy HTLV-1 provirus. HTLV-1 dysregulates many host genes by expressing a transcriptional transactivator, Tax, but it remains unknown whether HTLV-1 also alters host gene expression by insertional mutagenesis. In recent work (Satou et al, submitted) we have shown that HTLV-1 encodes a functional binding site for CCCTC binding factor (CTCF), a known mediator of chromatin looping. We hypothesize that the HTLV-1 provirus forms CTCF-mediated chromatin loops with the flanking host genome and dysregulates the expression of host genes. To test this hypothesis, we performed a circular chromatin conformation capture assay followed by high-throughput sequencing (4C-seq) which enables high resolution screening of physical long range interactions between chromosomes. Using the proviral CTCF site as bait, we have detected long-range interactions between the proviral and the host genome which suggest the formation of novel chromatin looping in clones of HTLV-1-infected T cells from both cases of ATL and from non-malignant cases of HTLV-1 infection. Chromosome conformation capture using specific primers (3C) confirmed clone-specific interactions. We are now testing whether these long-range interactions are associated with clone-specific alterations in the expression of host genes.
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.