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ミウラ ミチ
Michi Miura
三浦 未知 所属 川崎医科大学 医学部 基礎医学 微生物学 職種 助教 |
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| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | Epigenetic changes around the pX region and spontaneous HTLV-1 transcription are CTCF-independent. |
| 掲載誌名 | 正式名：Wellcome open research 略 称：Wellcome Open Res ISSNコード：2398502X/2398502X |
| 掲載区分 | 国外 |
| 巻・号・頁 | 3,pp.105 |
| 著者・共著者 | Miura Michi, Miyazato Paola, Satou Yorifumi, Tanaka Yuetsu, Bangham Charles R M |
| 担当区分 | 筆頭著者 |
| 発行年月 | 2018/12 |
| 概要 | Background: The human retrovirus HTLV-1 inserts the viral complementary DNA of 9 kb into the host genome. Both plus- and minus-strands of the provirus are transcribed, respectively from the 5' and 3' long terminal repeats (LTR). Plus-strand expression is rapid and intense once activated, whereas the minus-strand is transcribed at a lower, more constant level. To identify how HTLV-1 transcription is regulated, we investigated the epigenetic modifications associated with the onset of spontaneous plus-strand expression and the potential impact of the host factor CTCF. Methods: Patient-derived peripheral blood mononuclear cells (PBMCs) and in vitro HTLV-1-infected T cell clones were examined. Cells were stained for the plus-strand-encoded viral protein Tax, and sorted into Tax + and Tax - populations. Chromatin immunoprecipitation and methylated DNA immunoprecipitation were performed to identify epigenetic modifications in the provirus. Bisulfite-treated DNA fragments from the HTLV-1 LTRs were sequenced. Single-molecule RNA-FISH was performed, targeting HTLV-1 transcripts, for the estimation of transcription kinetics. The CRISPR/Cas9 technique was applied to alter the CTCF-binding site in the provirus, to test the impact of CTCF on the epigenetic modifications. Results: Changes in the histone modifications H3K4me3, H3K9Ac and H3K27Ac were strongly correlated with plus-strand expression. DNA in the body of the provirus was largely methylated except for the pX and 3' LTR regions, regardless of Tax expression. The plus-strand promoter was hypomethylated when Tax was expressed. Removal of CTCF had no discernible impact on the viral transcription or epigenetic modifications. Conclusions: The histone modifications H3K4me3, H3K9Ac and H3K27Ac are highly dynamic in the HTLV-1 provirus: they show rapid change with the onset of Tax expression, and are reversible. The HTLV-1 provirus has an intrinsic pattern of epigenetic modifications that is independent of both the provirus inse |
| DOI | 10.12688/wellcomeopenres.14741.2 |
| PMID | 30607369 |