| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Fukuda, Asami Yaguchi, Hiroko Bangham, Charles R. M. Miyazato, Paola Rowan, Aileen G. Satou, Yorifumi Watanabe, Takehisa Nakao, Mitsuyoshi Nosaka, Kisato Ishihara, Ko Melamed, Anat Miura, Michi |
| Description |
Author Affiliation: Satou Y ( Section of Virology, Division of Infectious Diseases, Imperial College, London W2 1PG, United Kingdom); Miyazato P ( Centre for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan); Ishihara K ( Priority Organization for Innovation and Excellence, Kumamoto University, Kumamoto 860-0811, Japan); Yaguchi H ( Section of Virology, Division of Infectious Diseases, Imperial College, London W2 1PG, United Kingdom); Melamed A ( Section of Virology, Division of Infectious Diseases, Imperial College, London W2 1PG, United Kingdom); Miura M ( Section of Virology, Division of Infectious Diseases, Imperial College, London W2 1PG, United Kingdom); Fukuda A ( Centre for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan); Nosaka K ( Cancer Centre, Kumamoto University Hospital, Kumamoto University, Kumamoto 860-0811, Japan); Watanabe T ( Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan.); Rowan AG ( Section of Virology, Division of Infectious Diseases, Imperial College, London W2 1PG, United Kingdom); Nakao M ( Core Research for Evolutionary Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan); Bangham CR ( Section of Virology, Division of Infectious Diseases, Imperial College, London W2 1PG, United Kingdom); |
| Abstract |
Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes malignant and inflammatory diseases in â ¼10% of infected people. A typical host has between 10(4) and 10(5) clones of HTLV-1-infected T lymphocytes, each clone distinguished by the genomic integration site of the single-copy HTLV-1 provirus. The HTLV-1 bZIP (HBZ) factor gene is constitutively expressed from the minus strand of the provirus, whereas plus-strand expression, required for viral propagation to uninfected cells, is suppressed or intermittent in vivo, allowing escape from host immune surveillance. It remains unknown what regulates this pattern of proviral transcription and latency. Here, we show that CTCF, a key regulator of chromatin structure and function, binds to the provirus at a sharp border in epigenetic modifications in the pX region of the HTLV-1 provirus in T cells naturally infected with HTLV-1. CTCF is a zinc-finger protein that binds to an insulator region in genomic DNA and plays a fundamental role in controlling higher order chromatin structure and gene expression in vertebrate cells. We show that CTCF bound to HTLV-1 acts as an enhancer blocker, regulates HTLV-1 mRNA splicing, and forms long-distance interactions with flanking host chromatin. CTCF-binding sites (CTCF-BSs) have been propagated throughout the genome by transposons in certain primate lineages, but CTCF binding has not previously been described in present-day exogenous retroviruses. The presence of an ectopic CTCF-BS introduced by the retrovirus in tens of thousands of genomic locations has the potential to cause widespread abnormalities in host cell chromatin structure and gene expression. |
| ISSN |
00278424 |
| e-ISSN |
10916490 |
| Journal |
Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number |
11 |
| Volume Number |
113 |
| Language |
English |
| Publisher |
National Academy of Sciences |
| Publisher Date |
2016-06-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Epigenesis, Genetic Genome, Human HTLV-I Infections Genetics Human T-lymphotropic Virus 1 Mutagenesis, Insertional Proviruses Repressor Proteins Metabolism Transcription Factors Viral Regulatory And Accessory Proteins Virus Integration Basic-Leucine Zipper Transcription Factors Biosynthesis Binding Sites CD4-Positive T-Lymphocytes Virology Chromatin Ultrastructure Chromatin Immunoprecipitation Consensus Sequence DNA DNA Methylation DNA, Viral Gene Expression Regulation, Viral Histone Code Protein Binding Retroviridae Proteins Transcription, Genetic Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Multidisciplinary |
