Epigenetic profiling in CD4+and CD8+T cells from Graves' disease patients reveals changes in genes associated with T cell receptor signaling

Limbach, MaiaInst Biomed & Translat Med, Mol Pathol, Tartu, Estonia. (författare)

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 decreased levels 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.

Saare, MarioInst Biomed & Translat Med, Mol Pathol, Tartu, Estonia. (författare)
Tserel, LiinaInst Biomed & Translat Med, Mol Pathol, Tartu, Estonia. (författare)
Kisand, KaiInst Biomed & Translat Med, Mol Pathol, Tartu, Estonia. (författare)
Eglit, TrimUniv Tartu, Dept Internal Med, Ulikooli 18, EE-50090 Tartu, Estonia.;Tartu Univ Hosp, Internal Med Clin, Tartu, Estonia. (författare)
Sauer, SaschaMax Planck Inst Mol Genet, Ihnestr 73, D-14195 Berlin, Germany. (författare)
Axelsson, TomasUppsala universitet,Institutionen för medicinska vetenskaper(Swepub:uu)toaxe957 (författare)
Syvänen, Ann-ChristineUppsala universitet,Molekylär medicin(Swepub:uu)anncsyva (författare)
Metspalu, AndresUniv Tartu, Inst Mol & Cell Biol, Estonian Genome Ctr, Ulikooli 18, EE-50090 Tartu, Estonia. (författare)
Milani, LiliUniv Tartu, Inst Mol & Cell Biol, Estonian Genome Ctr, Ulikooli 18, EE-50090 Tartu, Estonia. (författare)
Peterson, PaertInst Biomed & Translat Med, Mol Pathol, Tartu, Estonia. (författare)
Inst Biomed & Translat Med, Mol Pathol, Tartu, Estonia.Univ Tartu, Dept Internal Med, Ulikooli 18, EE-50090 Tartu, Estonia.;Tartu Univ Hosp, Internal Med Clin, Tartu, Estonia. (creator_code:org_t)

Av författaren/redakt...: Limbach, Maia; Saare, Mario; Tserel, Liina; Kisand, Kai; Eglit, Trim; Sauer, Sascha; visa fler...; Axelsson, Tomas; Syvänen, Ann-Chr ...; Metspalu, Andres; Milani, Lili; Peterson, Paert; visa färre...

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