STAT3 and SOX-5 induce BRG1-mediated chromatin remodeling of RORCE2 in Th17 cells
Abstract Retinoid-related orphan receptor gamma t (RORγt) is the lineage-specific transcription factor for T helper 17 (Th17) cells. Our previous study demonstrated that STAT3 likely participates in the activation of RORCE2 (a novel enhancer of the RORγt gene) in Th17 cells. However, the detailed me...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-01-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-05735-9 |
| _version_ | 1797362973982851072 |
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| author | Xian Wang Chao Han Di Yang Jian Zhou Hui Dong Zhiyuan Wei Shuai Xu Chen Xu Yiwei Zhang Yi Sun Bing Ni Sheng Guo Jingbo Zhang Tingting Zhao Xiangmei Chen Jie Luo Yuzhang Wu Yi Tian |
| author_facet | Xian Wang Chao Han Di Yang Jian Zhou Hui Dong Zhiyuan Wei Shuai Xu Chen Xu Yiwei Zhang Yi Sun Bing Ni Sheng Guo Jingbo Zhang Tingting Zhao Xiangmei Chen Jie Luo Yuzhang Wu Yi Tian |
| author_sort | Xian Wang |
| collection | DOAJ |
| description | Abstract Retinoid-related orphan receptor gamma t (RORγt) is the lineage-specific transcription factor for T helper 17 (Th17) cells. Our previous study demonstrated that STAT3 likely participates in the activation of RORCE2 (a novel enhancer of the RORγt gene) in Th17 cells. However, the detailed mechanism is still unclear. Here, we demonstrate that both STAT3 and SOX-5 mediate the enhancer activity of RORCE2 in vitro. Deletion of the STAT3 binding site (STAT3-BS) in RORCE2 impaired RORγt expression and Th17 differentiation, resulting in reduced severity of experimental autoimmune encephalomyelitis (EAE). Mechanistically, STAT3 and SOX-5 bind the RORCE2 region and recruit the chromatin remodeling factor BRG1 to remodel the nucleosomes positioned at this region. Collectively, our data suggest that STAT3 and SOX-5 mediate the differentiation of Th17 cells through the induction of BRG1-mediated chromatin remodeling of RORCE2 in Th17 cells. |
| first_indexed | 2024-03-08T16:14:44Z |
| format | Article |
| id | doaj.art-cc89d00d7f124079800da8b82fff0065 |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-03-08T16:14:44Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-cc89d00d7f124079800da8b82fff00652024-01-07T12:40:19ZengNature PortfolioCommunications Biology2399-36422024-01-017111010.1038/s42003-023-05735-9STAT3 and SOX-5 induce BRG1-mediated chromatin remodeling of RORCE2 in Th17 cellsXian Wang0Chao Han1Di Yang2Jian Zhou3Hui Dong4Zhiyuan Wei5Shuai Xu6Chen Xu7Yiwei Zhang8Yi Sun9Bing Ni10Sheng Guo11Jingbo Zhang12Tingting Zhao13Xiangmei Chen14Jie Luo15Yuzhang Wu16Yi Tian17Institute of Immunology, Third Military Medical University (Army Medical University)Institute of Immunology, Third Military Medical University (Army Medical University)Institute of Immunology, Third Military Medical University (Army Medical University)Institute of Immunology, Third Military Medical University (Army Medical University)Institute of Immunology, Third Military Medical University (Army Medical University)The First Affiliated Hospital, Third Military Medical University (Army Medical University)The Second Affiliated Hospital, Third Military Medical University (Army Medical University)Institute of Immunology, Third Military Medical University (Army Medical University)Institute of Immunology, Third Military Medical University (Army Medical University)The First Affiliated Hospital, Third Military Medical University (Army Medical University)Department of Pathophysiology, Third Military Medical University (Army Medical University)Institute of Immunology, Third Military Medical University (Army Medical University)The Second Affiliated Hospital, Third Military Medical University (Army Medical University)Chongqing International Institute for ImmunologyDepartment of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney DiseasesThe First Affiliated Hospital, Third Military Medical University (Army Medical University)Institute of Immunology, Third Military Medical University (Army Medical University)Institute of Immunology, Third Military Medical University (Army Medical University)Abstract Retinoid-related orphan receptor gamma t (RORγt) is the lineage-specific transcription factor for T helper 17 (Th17) cells. Our previous study demonstrated that STAT3 likely participates in the activation of RORCE2 (a novel enhancer of the RORγt gene) in Th17 cells. However, the detailed mechanism is still unclear. Here, we demonstrate that both STAT3 and SOX-5 mediate the enhancer activity of RORCE2 in vitro. Deletion of the STAT3 binding site (STAT3-BS) in RORCE2 impaired RORγt expression and Th17 differentiation, resulting in reduced severity of experimental autoimmune encephalomyelitis (EAE). Mechanistically, STAT3 and SOX-5 bind the RORCE2 region and recruit the chromatin remodeling factor BRG1 to remodel the nucleosomes positioned at this region. Collectively, our data suggest that STAT3 and SOX-5 mediate the differentiation of Th17 cells through the induction of BRG1-mediated chromatin remodeling of RORCE2 in Th17 cells.https://doi.org/10.1038/s42003-023-05735-9 |
| spellingShingle | Xian Wang Chao Han Di Yang Jian Zhou Hui Dong Zhiyuan Wei Shuai Xu Chen Xu Yiwei Zhang Yi Sun Bing Ni Sheng Guo Jingbo Zhang Tingting Zhao Xiangmei Chen Jie Luo Yuzhang Wu Yi Tian STAT3 and SOX-5 induce BRG1-mediated chromatin remodeling of RORCE2 in Th17 cells Communications Biology |
| title | STAT3 and SOX-5 induce BRG1-mediated chromatin remodeling of RORCE2 in Th17 cells |
| title_full | STAT3 and SOX-5 induce BRG1-mediated chromatin remodeling of RORCE2 in Th17 cells |
| title_fullStr | STAT3 and SOX-5 induce BRG1-mediated chromatin remodeling of RORCE2 in Th17 cells |
| title_full_unstemmed | STAT3 and SOX-5 induce BRG1-mediated chromatin remodeling of RORCE2 in Th17 cells |
| title_short | STAT3 and SOX-5 induce BRG1-mediated chromatin remodeling of RORCE2 in Th17 cells |
| title_sort | stat3 and sox 5 induce brg1 mediated chromatin remodeling of rorce2 in th17 cells |
| url | https://doi.org/10.1038/s42003-023-05735-9 |
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