Integrative analysis of ATAC-seq and RNA-seq for cells infected by human T-cell leukemia virus type 1.
Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy (HAM) after a long latent period in a fraction of infected individuals. These HTLV-1-infected cells typically have phenotypes similar to that of CD4+T cells, but the cell status is not wel...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1012690 |
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| author | Azusa Tanaka Yasuhiro Ishitsuka Hiroki Ohta Norihiro Takenouchi Masanori Nakagawa Ki-Ryang Koh Chiho Onishi Hiromitsu Tanaka Akihiro Fujimoto Jun-Ichirou Yasunaga Masao Matsuoka |
| author_facet | Azusa Tanaka Yasuhiro Ishitsuka Hiroki Ohta Norihiro Takenouchi Masanori Nakagawa Ki-Ryang Koh Chiho Onishi Hiromitsu Tanaka Akihiro Fujimoto Jun-Ichirou Yasunaga Masao Matsuoka |
| author_sort | Azusa Tanaka |
| collection | DOAJ |
| description | Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy (HAM) after a long latent period in a fraction of infected individuals. These HTLV-1-infected cells typically have phenotypes similar to that of CD4+T cells, but the cell status is not well understood. To extract the inherent information of HTLV-1-infected CD4+ cells, we integratively analyzed the ATAC-seq and RNA-seq data of the infected cells. Compared to CD4+T cells from healthy donors, we found anomalous chromatin accessibility in HTLV-1infected CD4+ cells derived from ATL cases in terms of location and sample-to-sample fluctuations in open chromatin regions. Further, by focusing on systematically selected genes near the open chromatin regions, we quantified the difference between the infected CD4+ cells in ATL cases and healthy CD4+T cells in terms of the correlation between the chromatin structures and the gene expressions. Based on a further analysis of chromatin accessibility, we detected TLL1 (Tolloid Like 1) as one of the key genes that exhibit unique gene expressions in ATL cases. A luciferase assay indicated that TLL1 has an isoform-dependent regulatory effect on TGF-β. Overall, this study provides results about the status of HTLV-1-infected cells, which are qualitatively consistent across the different scales of chromatin accessibility, transcription, and immunophenotype. |
| format | Article |
| id | doaj-art-2f31d6d4edce48949dbdf92965b9aea2 |
| institution | Kabale University |
| issn | 1553-734X 1553-7358 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj-art-2f31d6d4edce48949dbdf92965b9aea22025-02-05T05:30:39ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582025-01-01211e101269010.1371/journal.pcbi.1012690Integrative analysis of ATAC-seq and RNA-seq for cells infected by human T-cell leukemia virus type 1.Azusa TanakaYasuhiro IshitsukaHiroki OhtaNorihiro TakenouchiMasanori NakagawaKi-Ryang KohChiho OnishiHiromitsu TanakaAkihiro FujimotoJun-Ichirou YasunagaMasao MatsuokaHuman T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy (HAM) after a long latent period in a fraction of infected individuals. These HTLV-1-infected cells typically have phenotypes similar to that of CD4+T cells, but the cell status is not well understood. To extract the inherent information of HTLV-1-infected CD4+ cells, we integratively analyzed the ATAC-seq and RNA-seq data of the infected cells. Compared to CD4+T cells from healthy donors, we found anomalous chromatin accessibility in HTLV-1infected CD4+ cells derived from ATL cases in terms of location and sample-to-sample fluctuations in open chromatin regions. Further, by focusing on systematically selected genes near the open chromatin regions, we quantified the difference between the infected CD4+ cells in ATL cases and healthy CD4+T cells in terms of the correlation between the chromatin structures and the gene expressions. Based on a further analysis of chromatin accessibility, we detected TLL1 (Tolloid Like 1) as one of the key genes that exhibit unique gene expressions in ATL cases. A luciferase assay indicated that TLL1 has an isoform-dependent regulatory effect on TGF-β. Overall, this study provides results about the status of HTLV-1-infected cells, which are qualitatively consistent across the different scales of chromatin accessibility, transcription, and immunophenotype.https://doi.org/10.1371/journal.pcbi.1012690 |
| spellingShingle | Azusa Tanaka Yasuhiro Ishitsuka Hiroki Ohta Norihiro Takenouchi Masanori Nakagawa Ki-Ryang Koh Chiho Onishi Hiromitsu Tanaka Akihiro Fujimoto Jun-Ichirou Yasunaga Masao Matsuoka Integrative analysis of ATAC-seq and RNA-seq for cells infected by human T-cell leukemia virus type 1. PLoS Computational Biology |
| title | Integrative analysis of ATAC-seq and RNA-seq for cells infected by human T-cell leukemia virus type 1. |
| title_full | Integrative analysis of ATAC-seq and RNA-seq for cells infected by human T-cell leukemia virus type 1. |
| title_fullStr | Integrative analysis of ATAC-seq and RNA-seq for cells infected by human T-cell leukemia virus type 1. |
| title_full_unstemmed | Integrative analysis of ATAC-seq and RNA-seq for cells infected by human T-cell leukemia virus type 1. |
| title_short | Integrative analysis of ATAC-seq and RNA-seq for cells infected by human T-cell leukemia virus type 1. |
| title_sort | integrative analysis of atac seq and rna seq for cells infected by human t cell leukemia virus type 1 |
| url | https://doi.org/10.1371/journal.pcbi.1012690 |
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