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Chromatin remodeling factor, INO80, inhibits PMAIP1 in renal tubular cells via exchange of histone variant H2A.Z. for H2A
Epigenetic modifications such as DNA methylation, histone modifications, and chromatin structures in the kidney contribute towards the progression of chronic kidney disease (CKD). In this study, the role of chromatin remodeling factor inositol requiring 80 (INO80) was investigated. Although INO80 re...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10425331/ https://www.ncbi.nlm.nih.gov/pubmed/37580530 http://dx.doi.org/10.1038/s41598-023-40540-8 |
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author | Miura, Rika Mimura, Imari Saigusa, Hanako Yamazaki, Tomotaka Tanemoto, Fumiaki Kurata, Yu Sato, Dai Tanaka, Tetsuhiro Nangaku, Masaomi |
author_facet | Miura, Rika Mimura, Imari Saigusa, Hanako Yamazaki, Tomotaka Tanemoto, Fumiaki Kurata, Yu Sato, Dai Tanaka, Tetsuhiro Nangaku, Masaomi |
author_sort | Miura, Rika |
collection | PubMed |
description | Epigenetic modifications such as DNA methylation, histone modifications, and chromatin structures in the kidney contribute towards the progression of chronic kidney disease (CKD). In this study, the role of chromatin remodeling factor inositol requiring 80 (INO80) was investigated. Although INO80 regulates transcription by altering the chromatin structure at the nucleosome level, its role in the kidney remains unknown. We demonstrated that the expression of INO80 in impaired kidneys decreased in rats with unilateral urethral obstruction. We investigated INO80 expression in a proximal tubular cell line and observed that its expression decreased under hypoxic condition. Additionally, INO80 knockdown promoted apoptosis, suggesting that INO80 plays a role in inhibiting tubular cell apoptosis. We identified downstream target genes of INO80 via genome-wide analysis using RNA-sequences and found that the expression of apoptosis-related genes, such as TP53 and E2F1, and pro-apoptotic genes, such as PMAIP1, increased upon INO80 knockdown. ChIP-qPCR of the loci of PMAIP1 showed that the amount of H2A.Z. increased instead of decreasing the amount of H2A when INO80 was knocked down. These results indicated that INO80 plays a role in the exchange of H2A.Z. for H2A in the promoter region of PMAIP1 in tubular cells to inhibit apoptosis during CKD progression. |
format | Online Article Text |
id | pubmed-10425331 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-104253312023-08-16 Chromatin remodeling factor, INO80, inhibits PMAIP1 in renal tubular cells via exchange of histone variant H2A.Z. for H2A Miura, Rika Mimura, Imari Saigusa, Hanako Yamazaki, Tomotaka Tanemoto, Fumiaki Kurata, Yu Sato, Dai Tanaka, Tetsuhiro Nangaku, Masaomi Sci Rep Article Epigenetic modifications such as DNA methylation, histone modifications, and chromatin structures in the kidney contribute towards the progression of chronic kidney disease (CKD). In this study, the role of chromatin remodeling factor inositol requiring 80 (INO80) was investigated. Although INO80 regulates transcription by altering the chromatin structure at the nucleosome level, its role in the kidney remains unknown. We demonstrated that the expression of INO80 in impaired kidneys decreased in rats with unilateral urethral obstruction. We investigated INO80 expression in a proximal tubular cell line and observed that its expression decreased under hypoxic condition. Additionally, INO80 knockdown promoted apoptosis, suggesting that INO80 plays a role in inhibiting tubular cell apoptosis. We identified downstream target genes of INO80 via genome-wide analysis using RNA-sequences and found that the expression of apoptosis-related genes, such as TP53 and E2F1, and pro-apoptotic genes, such as PMAIP1, increased upon INO80 knockdown. ChIP-qPCR of the loci of PMAIP1 showed that the amount of H2A.Z. increased instead of decreasing the amount of H2A when INO80 was knocked down. These results indicated that INO80 plays a role in the exchange of H2A.Z. for H2A in the promoter region of PMAIP1 in tubular cells to inhibit apoptosis during CKD progression. Nature Publishing Group UK 2023-08-14 /pmc/articles/PMC10425331/ /pubmed/37580530 http://dx.doi.org/10.1038/s41598-023-40540-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Miura, Rika Mimura, Imari Saigusa, Hanako Yamazaki, Tomotaka Tanemoto, Fumiaki Kurata, Yu Sato, Dai Tanaka, Tetsuhiro Nangaku, Masaomi Chromatin remodeling factor, INO80, inhibits PMAIP1 in renal tubular cells via exchange of histone variant H2A.Z. for H2A |
title | Chromatin remodeling factor, INO80, inhibits PMAIP1 in renal tubular cells via exchange of histone variant H2A.Z. for H2A |
title_full | Chromatin remodeling factor, INO80, inhibits PMAIP1 in renal tubular cells via exchange of histone variant H2A.Z. for H2A |
title_fullStr | Chromatin remodeling factor, INO80, inhibits PMAIP1 in renal tubular cells via exchange of histone variant H2A.Z. for H2A |
title_full_unstemmed | Chromatin remodeling factor, INO80, inhibits PMAIP1 in renal tubular cells via exchange of histone variant H2A.Z. for H2A |
title_short | Chromatin remodeling factor, INO80, inhibits PMAIP1 in renal tubular cells via exchange of histone variant H2A.Z. for H2A |
title_sort | chromatin remodeling factor, ino80, inhibits pmaip1 in renal tubular cells via exchange of histone variant h2a.z. for h2a |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10425331/ https://www.ncbi.nlm.nih.gov/pubmed/37580530 http://dx.doi.org/10.1038/s41598-023-40540-8 |
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