BioProject

In Graves’ disease (GD), a combination of genetic, epigenetic and environmental factors causes an autoimmune response to the thyroid gland, characterized by lymphocytic infiltrations and autoantibodies targeting the thyroid stimulating hormone receptor (TSHR) and other thyroid antigens. More...

In Graves’ disease (GD), a combination of genetic, epigenetic and environmental factors causes an autoimmune response to the thyroid gland, characterized by lymphocytic infiltrations and autoantibodies targeting the thyroid stimulating hormone receptor (TSHR) and other thyroid antigens. To identify the epigenetic changes involved in GD, we performed a genome-wide analysis of DNA methylation and enrichment of H3K4me3 and H3K27ac histone marks in sorted CD4+ and CD8+ T cells. We found 365 and 3322 differentially methylated CpG sites in CD4+ and CD8+ T cells, respectively. Among the hypermethylated CpG sites, we specifically found enrichment of genes involved in T cell signaling (CD247, LCK, ZAP70, CD3D, CD3E, CD3G, CTLA4 and CD8A) and decreased expression of CD3 gene family members. The hypermethylation was accompanied with the active chromatin histone modifications as we found decreased signals of H3K4me3 and H3K27ac marks at several T cell signaling genes in ChIP-seq analysis. In addition, we found hypermethylation of the TSHR gene first intron, where several GD-associated polymorphisms are located. Our results demonstrate an involvement of dysregulated DNA methylation and histone modifications at T cell signaling genes in GD patients. Overall design: Individuals were recruited from the Estonian Genome Center of the University of Tartu. Genomic DNA was extracted from sorted CD4+ (H3K4me3 ChIP: 15 controls and 14 GD patients; H3K27ac ChIP: 11 controls and 13 GD patients) and CD8+ (H3K4me3 ChIP: 17 controls and 14 GD patients; H3K27ac ChIP: 15 controls and 14 GD patients) T cells. The data collection was performed at the SNP&SEQ Technology Platform in Uppsala University, and data analysis was done at the Institute of Biomedicine and Translational Medicine in the University of Tartu. Less...