22 results found
Bangham CRM, Melamed A, Yaguchi H, et al., 2018, The human leukemia virus HTLV-1 alters the structure and transcription of host chromatin in cis, eLife, Vol: 7, Pages: 1-20, ISSN: 2050-084X
Chromatin looping controls gene expression by regulating promoter-enhancer contacts, the spread of epigenetic modifications, and the segregation of the genome into transcriptionally active and inactive compartments. We studied the impact on the structure and expression of host chromatin by the human retrovirus HTLV-1. We show that HTLV-1 disrupts host chromatin structure by forming loops between the provirus and the host genome; certain loops depend on the critical chromatin architectural protein CTCF, which we recently discovered binds to the HTLV-1 provirus. We show that the provirus causes two distinct patterns of abnormal transcription of the host genome in cis: bidirectional transcription in the host genome immediately flanking the provirus, and clone-specific transcription in cis at non-contiguous loci up to >300 kb from the integration site. We conclude that HTLV-1 causes insertional mutagenesis up to the megabase range in the host genome in >104 persistently-maintained HTLV-1+ T-cell clones in vivo.
Human T-lymphotropic virus type-1 (HTLV-1) is the causative agent of adult T-cell leukaemia/lymphoma (ATL), an aggressive CD4+ T-cell malignancy. The mechanisms of leukaemogenesis in ATL are incompletely understood. Insertional mutagenesis has not previously been thought to contribute to the pathogenesis of ATL. However, the recent discovery that HTLV-1 binds the key chromatin architectural protein CTCF raises the hypothesis that HTLV-1 deregulates host gene expression by causing abnormal chromatin looping, bringing the strong HTLV-1 promoter-enhancer near to host genes that lie up to 2Mb from the integrated provirus. Here we review current opinion on the mechanisms of oncogenesis in ATL, with particular emphasis on the local and distant impact of HTLV-1 on the structure and expression of the host genome.
Satou Y, Miyazato P, Ishihara Y, et al., 2016, The retrovirus HTLV-1 inserts an ectopic CTCF-binding site into the human genome, Proceedings of the National Academy of Sciences of the United States of America, Vol: 113, Pages: 3054-3059, ISSN: 0027-8424
Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus thatcauses malignant and inflammatory diseases in 10% of infectedpeople. A typical host has between 104and 105clones of HTLV-1-infected T lymphocytes, each clone distinguished by the genomicintegration site of the single-copy HTLV-1 provirus. TheHBZgeneis constitutively expressed from the minus strand of the provirus,whereas plus-strand expression, required for viral propagation touninfected cells, is suppressed or intermittentin vivo, allowingescape from host immune surveillance. It remains unknown whatregulates this pattern of proviral transcription and latency. Herewe show that CTCF, a key regulator of chromatin structure andfunction, binds to the provirus at a sharp border in epigeneticmodifications in the pX region of the HTLV-1 provirus, in T cellsnaturally infected with HTLV-1. CTCF is a zinc-finger protein thatbinds to an insulator region in genomic DNA and plays a funda-mental role in controlling higher-order chromatin structure andgene expression in vertebrate cells. We show that CTCF boundto HTLV-1 acts as an enhancer blocker, regulates HTLV-1 mRNAsplicing, and forms long-distance interactions with flanking hostchromatin. CTCF binding sites have been propagated through-out the genome by transposons in certain primate lineages, butCTCF binding has not previously been described in present-dayexogenous retroviruses. The presence of an ectopic CTCF bindingsite introduced by the retrovirus in tens of thousands of genomiclocations has the potential to cause widespread abnormalities inhost cell chromatin structure and gene expression.
Melamed A, Yaguchi H, Rowan A, et al., 2015, Comparative analysis of gene expression patterns in the HTLV-1 infected T-cell clones, Publisher: BIOMED CENTRAL LTD, ISSN: 1742-4690
Yaguchi H, Melamed A, Rowan A, et al., 2015, Identification of long-range chromatin interactions between HTLV-1 and the host genome, Publisher: BIOMED CENTRAL LTD, ISSN: 1742-4690
Eguren M, Alvarez-Fernandez M, Garcia F, et al., 2014, A Synthetic Lethal Interaction between APC/C and Topoisomerase Poisons Uncovered by Proteomic Screens, CELL REPORTS, Vol: 6, Pages: 670-683, ISSN: 2211-1247
Shimazu S, Nagamura Y, Yaguchi H, et al., 2011, Correlation of mutant menin stability with clinical expression of multiple endocrine neoplasia type 1 and its incomplete forms, CANCER SCIENCE, Vol: 102, Pages: 2097-2102, ISSN: 1347-9032
Kitoh A, Ono M, Naoe Y, et al., 2009, Indispensable Role of the Runx1-Cbf beta Transcription Complex for In Vivo-Suppressive Function of FoxP3(+) Regulatory T Cells, IMMUNITY, Vol: 31, Pages: 609-620, ISSN: 1074-7613
Ono M, Yaguchi H, Ohkura N, et al., 2007, Foxp3 controls regulatory T-cell function by interacting with AML1/Runx1, NATURE, Vol: 446, Pages: 685-689, ISSN: 0028-0836
Fukuuchi A, Nagamura Y, Yaguchi H, et al., 2006, A whole MEN1 gene deletion flanked by Alu repeats in a family with multiple endocrine neoplasia type 1, JAPANESE JOURNAL OF CLINICAL ONCOLOGY, Vol: 36, Pages: 739-744, ISSN: 0368-2811
Takahashi M, Kikuchi M, Ohkura N, et al., 2006, Detection of APC gene deletion by double competitive polymerase chain reaction in patients with familial adenomatous polyposis, INTERNATIONAL JOURNAL OF ONCOLOGY, Vol: 29, Pages: 413-421, ISSN: 1019-6439
Ohkura N, Takahashi M, Yaguchi H, et al., 2005, Coactivator-associated arginine methyltransferase 1, CARM1, affects pre-mRNA splicing in an isoform-specific manner, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 280, Pages: 28927-28935
Yaguchi H, Ohkura N, Takahashi M, et al., 2004, Menin missense mutants associated with multiple endocrine neoplasia type 1 are rapidly degraded via the ubiquitin-proteasome pathway, MOLECULAR AND CELLULAR BIOLOGY, Vol: 24, Pages: 6569-6580, ISSN: 0270-7306
Yaguchi H, Ohkura N, Tsukada T, et al., 2002, Menin, the multiple endocrine neoplasia type 1 gene product, exhibits GTP-hydrolyzing activity in the presence of the tumor metastasis suppressor nm23, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 277, Pages: 38197-38204, ISSN: 0021-9258
Nakahara T, Yaguchi H, Yoshida M, et al., 2002, Effects of exposure of CHO-K1 cells to a 10-T static magnetic field, RADIOLOGY, Vol: 224, Pages: 817-822, ISSN: 0033-8419
Ohkura N, Yaguchi H, Tsukada T, et al., 2002, The EWS/NOR1 fusion gene product gains a novel activity affecting pre-mRNA splicing, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 277, Pages: 535-543, ISSN: 0021-9258
Takimoto K, Yaguchi H, Miyakoshi J, 2001, Extremely low frequency magnetic fields suppress the reduction of germination rate of Arabidopsis thaliana seeds kept in saturated humidity, BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, Vol: 65, Pages: 2552-2554, ISSN: 0916-8451
Yaguchi H, Yoshida M, Ding GR, et al., 2000, Increased chromatid-type chromosomal aberrations in mouse m5S cells exposed to power-line frequency magnetic fields, INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, Vol: 76, Pages: 1677-1684, ISSN: 0955-3002
Ding GR, Yaguchi H, Yoshida M, et al., 2000, Increase in X-ray-induced mutations by exposure to magnetic field (60 Hz, 5 mT) in NF-kappa B-inhibited cells, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol: 276, Pages: 238-243, ISSN: 0006-291X
Miyakoshi J, Yoshida M, Yaguchi H, et al., 2000, Exposure to extremely low frequency magnetic fields suppresses X-ray-induced transformation in mouse C3H10T1/2 cells, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol: 271, Pages: 323-327, ISSN: 0006-291X
Miyakoshi J, Mori Y, Yaguchi H, et al., 2000, Suppression of heat-induced hsp-70 by simultaneous exposure to 50 mT magnetic field, LIFE SCIENCES, Vol: 66, Pages: 1187-1196, ISSN: 0024-3205
Yaguchi H, Yoshida M, Ejima Y, et al., 1999, Effect of high-density extremely low frequency magnetic field on sister chromatid exchanges in mouse m5S cells, MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS, Vol: 440, Pages: 189-194, ISSN: 1383-5718
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