HMGB1 Recruits TET2/AID/TDG to Induce DNA Demethylation in STAT3 Promoter in CD4+ T Cells from aGVHD Patients
STAT3 is highly expressed in aGVHD CD4+ T cells and plays a critical role in inducing or worsening aGVHD. In our preceding studies, DNA hypomethylation in STAT3 promoter was shown to cause high expression of STAT3 in aGVHD CD4+ T cells, and the process could be modulated by HMGB1, but the underlying...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-01-01
|
| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2020/7165230 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849396405695676416 |
|---|---|
| author | Xuejun Xu Yan Chen Enyi Liu Bin Fu Juan Hua Xu Chen Yajing Xu |
| author_facet | Xuejun Xu Yan Chen Enyi Liu Bin Fu Juan Hua Xu Chen Yajing Xu |
| author_sort | Xuejun Xu |
| collection | DOAJ |
| description | STAT3 is highly expressed in aGVHD CD4+ T cells and plays a critical role in inducing or worsening aGVHD. In our preceding studies, DNA hypomethylation in STAT3 promoter was shown to cause high expression of STAT3 in aGVHD CD4+ T cells, and the process could be modulated by HMGB1, but the underlying mechanism remains unclear. TET2, AID, and TDG are indispensable in DNA demethylation; meanwhile, TET2 and AID also serve extremely important roles in immune response. So, we speculated these enzymes involved in the STAT3 promoter hypomethylation induced by HMGB1 in aGVHD CD4+ T cells. In this study, we found that the binding levels of TET2/AID/TDG to STAT3 promoter were remarkably increased in CD4+T cells from aGVHD patients and were significantly negatively correlated with the STAT3 promoter methylation level. Simultaneously, we revealed that HMGB1 could recruit TET2, AID, and TDG to form a complex in the STAT3 promoter region. Interference with the expression of TET2/AID/TDG inhibited the overexpression of STAT3 caused by HMGB1 downregulation of the STAT3 promoter DNA methylation. These data demonstrated a new molecular mechanism of how HMGB1 promoted the expression of STAT3 in CD4+ T cells from aGVHD patients. |
| format | Article |
| id | doaj-art-b2992bf76c444d9699daee5815d4b18d |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-b2992bf76c444d9699daee5815d4b18d2025-08-20T03:39:21ZengWileyJournal of Immunology Research2314-88612314-71562020-01-01202010.1155/2020/71652307165230HMGB1 Recruits TET2/AID/TDG to Induce DNA Demethylation in STAT3 Promoter in CD4+ T Cells from aGVHD PatientsXuejun Xu0Yan Chen1Enyi Liu2Bin Fu3Juan Hua4Xu Chen5Yajing Xu6Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaSTAT3 is highly expressed in aGVHD CD4+ T cells and plays a critical role in inducing or worsening aGVHD. In our preceding studies, DNA hypomethylation in STAT3 promoter was shown to cause high expression of STAT3 in aGVHD CD4+ T cells, and the process could be modulated by HMGB1, but the underlying mechanism remains unclear. TET2, AID, and TDG are indispensable in DNA demethylation; meanwhile, TET2 and AID also serve extremely important roles in immune response. So, we speculated these enzymes involved in the STAT3 promoter hypomethylation induced by HMGB1 in aGVHD CD4+ T cells. In this study, we found that the binding levels of TET2/AID/TDG to STAT3 promoter were remarkably increased in CD4+T cells from aGVHD patients and were significantly negatively correlated with the STAT3 promoter methylation level. Simultaneously, we revealed that HMGB1 could recruit TET2, AID, and TDG to form a complex in the STAT3 promoter region. Interference with the expression of TET2/AID/TDG inhibited the overexpression of STAT3 caused by HMGB1 downregulation of the STAT3 promoter DNA methylation. These data demonstrated a new molecular mechanism of how HMGB1 promoted the expression of STAT3 in CD4+ T cells from aGVHD patients.http://dx.doi.org/10.1155/2020/7165230 |
| spellingShingle | Xuejun Xu Yan Chen Enyi Liu Bin Fu Juan Hua Xu Chen Yajing Xu HMGB1 Recruits TET2/AID/TDG to Induce DNA Demethylation in STAT3 Promoter in CD4+ T Cells from aGVHD Patients Journal of Immunology Research |
| title | HMGB1 Recruits TET2/AID/TDG to Induce DNA Demethylation in STAT3 Promoter in CD4+ T Cells from aGVHD Patients |
| title_full | HMGB1 Recruits TET2/AID/TDG to Induce DNA Demethylation in STAT3 Promoter in CD4+ T Cells from aGVHD Patients |
| title_fullStr | HMGB1 Recruits TET2/AID/TDG to Induce DNA Demethylation in STAT3 Promoter in CD4+ T Cells from aGVHD Patients |
| title_full_unstemmed | HMGB1 Recruits TET2/AID/TDG to Induce DNA Demethylation in STAT3 Promoter in CD4+ T Cells from aGVHD Patients |
| title_short | HMGB1 Recruits TET2/AID/TDG to Induce DNA Demethylation in STAT3 Promoter in CD4+ T Cells from aGVHD Patients |
| title_sort | hmgb1 recruits tet2 aid tdg to induce dna demethylation in stat3 promoter in cd4 t cells from agvhd patients |
| url | http://dx.doi.org/10.1155/2020/7165230 |
| work_keys_str_mv | AT xuejunxu hmgb1recruitstet2aidtdgtoinducednademethylationinstat3promoterincd4tcellsfromagvhdpatients AT yanchen hmgb1recruitstet2aidtdgtoinducednademethylationinstat3promoterincd4tcellsfromagvhdpatients AT enyiliu hmgb1recruitstet2aidtdgtoinducednademethylationinstat3promoterincd4tcellsfromagvhdpatients AT binfu hmgb1recruitstet2aidtdgtoinducednademethylationinstat3promoterincd4tcellsfromagvhdpatients AT juanhua hmgb1recruitstet2aidtdgtoinducednademethylationinstat3promoterincd4tcellsfromagvhdpatients AT xuchen hmgb1recruitstet2aidtdgtoinducednademethylationinstat3promoterincd4tcellsfromagvhdpatients AT yajingxu hmgb1recruitstet2aidtdgtoinducednademethylationinstat3promoterincd4tcellsfromagvhdpatients |