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BCL-6 suppresses miR-142-3p/5p expression in SLE CD4(+) T cells by modulating histone methylation and acetylation of the miR-142 promoter
The reduced expression of miR-142-3p/5p in CD4(+) T cells of SLE patients caused T cell hyperactivity and B cell hyperstimulation. This study aimed to investigate the mechanisms of regulating miR-142-3p/5p expression in SLE CD4(+) T cells. The BCL-6 expression was significantly increased in SLE CD4(...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192839/ https://www.ncbi.nlm.nih.gov/pubmed/31431691 http://dx.doi.org/10.1038/s41423-019-0268-3 |
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author | Ding, Shu Zhang, Qing Luo, Shuangyan Gao, Lihua Huang, Jinhua Lu, Jianyun Chen, Jing Zeng, Qinghai Guo, Aiyuan Zeng, Jinrong Lu, Qianjin |
author_facet | Ding, Shu Zhang, Qing Luo, Shuangyan Gao, Lihua Huang, Jinhua Lu, Jianyun Chen, Jing Zeng, Qinghai Guo, Aiyuan Zeng, Jinrong Lu, Qianjin |
author_sort | Ding, Shu |
collection | PubMed |
description | The reduced expression of miR-142-3p/5p in CD4(+) T cells of SLE patients caused T cell hyperactivity and B cell hyperstimulation. This study aimed to investigate the mechanisms of regulating miR-142-3p/5p expression in SLE CD4(+) T cells. The BCL-6 expression was significantly increased in SLE CD4(+) T cells compared with normal controls, and the BCL-6 expression was inversely correlated with miR-142-3p/5p expression. BCL-6 suppresses the expression of miR-142-3p/5p by increasing H3K27me3 level and reducing H3K9/K14ac levels in SLE CD4(+) T cells. BCL-6 regulates histone modifications in miR-142 promoter by recruiting EZH2 and HDAC5. Furthermore, we observed significantly decreased CD40L, ICOS, and IL-21 expression levels in SLE CD4(+) T cells with BCL-6 interference, and obviously reduced autoantibody IgG production in autologous B cells co-cultured with BCL-6 inhibited SLE CD4(+) T cells. Our study found that increased BCL-6 up-regulates H3K27me3 and down-regulates H3K9/14ac at miR-142 promoter in SLE CD4(+) T cells. These factors induce a declination in miR-142-3p/5p expression, consequently resulting in CD4(+) T cell hyperactivity. |
format | Online Article Text |
id | pubmed-7192839 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-71928392020-05-04 BCL-6 suppresses miR-142-3p/5p expression in SLE CD4(+) T cells by modulating histone methylation and acetylation of the miR-142 promoter Ding, Shu Zhang, Qing Luo, Shuangyan Gao, Lihua Huang, Jinhua Lu, Jianyun Chen, Jing Zeng, Qinghai Guo, Aiyuan Zeng, Jinrong Lu, Qianjin Cell Mol Immunol Article The reduced expression of miR-142-3p/5p in CD4(+) T cells of SLE patients caused T cell hyperactivity and B cell hyperstimulation. This study aimed to investigate the mechanisms of regulating miR-142-3p/5p expression in SLE CD4(+) T cells. The BCL-6 expression was significantly increased in SLE CD4(+) T cells compared with normal controls, and the BCL-6 expression was inversely correlated with miR-142-3p/5p expression. BCL-6 suppresses the expression of miR-142-3p/5p by increasing H3K27me3 level and reducing H3K9/K14ac levels in SLE CD4(+) T cells. BCL-6 regulates histone modifications in miR-142 promoter by recruiting EZH2 and HDAC5. Furthermore, we observed significantly decreased CD40L, ICOS, and IL-21 expression levels in SLE CD4(+) T cells with BCL-6 interference, and obviously reduced autoantibody IgG production in autologous B cells co-cultured with BCL-6 inhibited SLE CD4(+) T cells. Our study found that increased BCL-6 up-regulates H3K27me3 and down-regulates H3K9/14ac at miR-142 promoter in SLE CD4(+) T cells. These factors induce a declination in miR-142-3p/5p expression, consequently resulting in CD4(+) T cell hyperactivity. Nature Publishing Group UK 2019-08-20 2020-05 /pmc/articles/PMC7192839/ /pubmed/31431691 http://dx.doi.org/10.1038/s41423-019-0268-3 Text en © The Author(s) 2019 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Ding, Shu Zhang, Qing Luo, Shuangyan Gao, Lihua Huang, Jinhua Lu, Jianyun Chen, Jing Zeng, Qinghai Guo, Aiyuan Zeng, Jinrong Lu, Qianjin BCL-6 suppresses miR-142-3p/5p expression in SLE CD4(+) T cells by modulating histone methylation and acetylation of the miR-142 promoter |
title | BCL-6 suppresses miR-142-3p/5p expression in SLE CD4(+) T cells by modulating histone methylation and acetylation of the miR-142 promoter |
title_full | BCL-6 suppresses miR-142-3p/5p expression in SLE CD4(+) T cells by modulating histone methylation and acetylation of the miR-142 promoter |
title_fullStr | BCL-6 suppresses miR-142-3p/5p expression in SLE CD4(+) T cells by modulating histone methylation and acetylation of the miR-142 promoter |
title_full_unstemmed | BCL-6 suppresses miR-142-3p/5p expression in SLE CD4(+) T cells by modulating histone methylation and acetylation of the miR-142 promoter |
title_short | BCL-6 suppresses miR-142-3p/5p expression in SLE CD4(+) T cells by modulating histone methylation and acetylation of the miR-142 promoter |
title_sort | bcl-6 suppresses mir-142-3p/5p expression in sle cd4(+) t cells by modulating histone methylation and acetylation of the mir-142 promoter |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192839/ https://www.ncbi.nlm.nih.gov/pubmed/31431691 http://dx.doi.org/10.1038/s41423-019-0268-3 |
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