The impact of HTLV-1 expression on the 3D structure and expression of host chromatin.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science, c2005-

Human T-lymphotropic virus 1*/genetics ; Human T-lymphotropic virus 1*/metabolism; Chromatin/genetics ; Chromatin/metabolism ; Proviruses/genetics ; T-Lymphocytes

A typical HTLV-1-infected individual carries >104 different HTLV-1-infected T cell clones, each with a single-copy provirus integrated in a unique genomic site. We previously showed that the HTLV-1 provirus causes aberrant transcription in the flanking host genome and, by binding the chromatin architectural protein CTCF, forms abnormal chromatin loops with the host genome. However, it remained unknown whether these effects were exerted simply by the presence of the provirus or were induced by its transcription. To answer this question, we sorted HTLV-1-infected T-cell clones into cells positive or negative for proviral plus-strand expression, and then quantified host and provirus transcription using RNA-seq, and chromatin looping using quantitative chromosome conformation capture (q4C), in each cell population. We found that proviral plus-strand transcription induces aberrant transcription and splicing in the flanking genome but suppresses aberrant chromatin loop formation with the nearby host chromatin. Reducing provirus-induced host transcription with an inhibitor of transcriptional elongation allows recovery of chromatin loops in the plus-strand-expressing population. We conclude that aberrant host transcription induced by proviral expression causes temporary, reversible disruption of chromatin looping in the vicinity of the provirus.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Yaguchi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

PLoS Pathog. 2022 May 16;18(5):e1010387. (PMID: 35576236)
Cell. 2009 Jun 26;137(7):1194-211. (PMID: 19563753)
Blood. 2012 Oct 25;120(17):3488-90. (PMID: 22955925)
Front Genet. 2022 Mar 25;13:842860. (PMID: 35401663)
Nat Rev Mol Cell Biol. 2021 Jul;22(7):445-464. (PMID: 33767413)
Sci Transl Med. 2020 May 13;12(543):. (PMID: 32404504)
Nat Commun. 2022 May 3;13(1):2405. (PMID: 35504920)
Wellcome Open Res. 2017 Sep 22;2:87. (PMID: 29062917)
Proc Natl Acad Sci U S A. 2018 Feb 6;115(6):E1269-E1278. (PMID: 29358408)
PLoS Pathog. 2022 Nov 28;18(11):e1010774. (PMID: 36441826)
Sci Adv. 2022 Apr 29;8(17):eabm6210. (PMID: 35486737)
Nat Genet. 2015 Nov;47(11):1304-15. (PMID: 26437031)
Genome Biol. 2022 Nov 9;23(1):238. (PMID: 36352464)
J Cell Biol. 2017 Nov 6;216(11):3441-3452. (PMID: 28855250)
Methods. 2020 Jan 1;170:17-32. (PMID: 31351925)
Nat Commun. 2017 May 23;8:15264. (PMID: 28534499)
PLoS Comput Biol. 2020 Sep 17;16(9):e1007470. (PMID: 32941445)
Brief Funct Genomics. 2020 Mar 23;19(2):128-138. (PMID: 32025693)
Front Microbiol. 2018 Mar 19;9:449. (PMID: 29615991)
Cell. 2018 Sep 6;174(6):1522-1536.e22. (PMID: 30146161)
Nat Rev Genet. 2020 Apr;21(4):207-226. (PMID: 31848476)
Int J Cancer. 2004 Apr 20;109(4):559-67. (PMID: 14991578)
Proc Natl Acad Sci U S A. 2016 Mar 15;113(11):3054-9. (PMID: 26929370)
Proc Natl Acad Sci U S A. 2014 Jan 21;111(3):889-90. (PMID: 24398527)
Blood. 2011 Mar 17;117(11):3113-22. (PMID: 21228324)
PLoS Pathog. 2021 May 21;17(5):e1009577. (PMID: 34019588)
Elife. 2018 Jun 26;7:. (PMID: 29941091)
Wellcome Open Res. 2018 Aug 24;3:105. (PMID: 30607369)
Nat Rev Genet. 2018 Jul;19(7):453-467. (PMID: 29692413)

United Kingdom WT_ Wellcome Trust

0 (Chromatin)

Date Created: 20240301 Date Completed: 20240315 Latest Revision: 20240315

20240315

PMC10936777

10.1371/journal.ppat.1011716

38427693