Regulation of DNA demethylation of STAT3 promoter in CD4+ T cells from aGVHD patients by HMGB1/GADD45A / 中南大学学报(医学版)
Journal of Central South University(Medical Sciences)
;
(12): 937-944, 2018.
Article
in Chinese
| WPRIM
| ID: wpr-813170
ABSTRACT
To study the molecular mechanism for DNA hypomethylation of STAT3 promoter in CD4+ T cells from acute graft-versus-host disease (aGVHD) patients.
Methods:
We collected CD4+ T cells from peripheral blood of 42 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) from HLA-identical sibling donors. GADD45A expression level in CD4+ T cells was measured by real-time PCR and Western blot. The binding level between HMGB1 and GADD45A in CD4+ T cells was analyzed by co-immunoprecipitation, while the binding levels of HMGB1/GADD45A with STAT3 promoter were detected by chromatin immunoprecipitation-quantitative real-time PCR (ChIP-qPCR). After overexpression of HMGB1 and knockdown of GADD45A in normal CD4+ T cells, STAT3 expression and DNA methylation were measured by Western blot and bisulfite sequencing PCR, respectively.Results:
GADD45A expression was significantly up-regulated in patients with aGVHD compared with that in the patients without aGVHD. More HMGB1-GADD45A complexes were found in CD4+ T cells from patients with aGVHD compared with that in patients without aGVHD. The bindings of HMGB1/GADD45A with STAT3 promoter were significantly increased, and the binding levels of HMGB1/GADD45A were negatively correlated with STAT3 promoter DNA methylation. The expression of STAT3 was significantly reduced and the DNA methylation of STAT3 promoter was significantly increased in CD4+ T cells with overexpression of HMGB1 and knockdown of GADD45A compared with CD4+ T cells only with overexpression of HMGB1.Conclusion:
The increased expression of HMGB1/GADD45A plays an importent role in STAT3 promoter DNA hypomethylation, thereby promoting STAT3 expression in CD4+ T cells from aGVHD patients.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Nuclear Proteins
/
CD4-Positive T-Lymphocytes
/
Gene Expression Regulation
/
Promoter Regions, Genetic
/
Hematopoietic Stem Cell Transplantation
/
Cell Cycle Proteins
/
HMGB1 Protein
/
STAT3 Transcription Factor
/
DNA Demethylation
/
Genetics
Limits:
Humans
Language:
Chinese
Journal:
Journal of Central South University(Medical Sciences)
Year:
2018
Type:
Article
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