Elevated histone H3 acetylation is associated with genes involved in T lymphocyte activation and glutamate decarboxylase antibody production in patients with type 1 diabetes

组蛋白 H3 乙酰化升高与 1 型糖尿病患者中 T 淋巴细胞活化和谷氨酸脱羧酶抗体产生基因相关

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作者:Yanfei Wang, Can Hou, Jonathan Wisler, Kanhaiya Singh, Chao Wu, Zhiguo Xie, Qianjin Lu, Zhiguang Zhou

Conclusions

The present study generates a genome-wide histone acetylation profile specific to CD4+ T lymphocytes in type 1 diabetes patients who are glutamic acid decarboxylase antibody-positive, which is instrumental in improving our understanding of the epigenetic involvement in autoimmune diabetes.

Methods

A total of 12 patients with new-onset type 1 diabetes who were glutamate decarboxylase antibody-positive were enrolled, and 12 healthy individuals were recruited as controls. The global histone H3 acetylation level of CD4+ T lymphocytes from peripheral blood was detected by western blot, with chromatin immunoprecipitation linked to microarrays to characterize the promoter acetylation profile. Furthermore, we validated the

Results

Elevated global histone H3 acetylation level was observed in type 1 diabetes patients, with 607 differentially acetylated genes identified between type 1 diabetes patients and controls by chromatin immunoprecipitation linked to microarrays. The hyperacetylated genes were enriched in biological processes involved in immune cell activation and inflammatory response. Gene-specific assessments showed that increased transcription of inducible T-cell costimulator was in concordance with the elevated acetylation in its gene promoter, along with positive correlation with glutamate decarboxylase antibody titer in type 1 diabetes patients. Conclusions: The present study generates a genome-wide histone acetylation profile specific to CD4+ T lymphocytes in type 1 diabetes patients who are glutamic acid decarboxylase antibody-positive, which is instrumental in improving our understanding of the epigenetic involvement in autoimmune diabetes.

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