Introduction: The precise pathogenesis of Hashimoto's thyroiditis (HT) is yet to be fully elucidated. The role of epigenetics in the pathogenesis of HT has scarcely been addressed. Tri-methylated histone H3 lysine 4 (H3K4me3) is generally regarded as a marker of gene activation. The aim of this study was to explore genome-wide H3K4me3 patterns and global protein levels in primary thyrocytes and thyroids from HT patients.
Material and methods: Chromatin immunoprecipitation sequencing (ChIP-seq) was used to analyze genome-wide H3K4me3 patterns in primary cultured thyrocytes from three HT females and three age-matched female control subjects. Western blotting was used to analyze global H3K4me3 levels in thyrocytes and thyroid tissues. Gene expression was determined using RT-PCR. Mixed-lineage leukemia 1 (MLL1) protein levels were measured by western blotting and immunohistochemistry.
Results: Nine genes - TG, CXCL8, CCL2, CXCL10, FASLG, ICAM1, ITGA4, IL18 and TRAIL - showed increased H3K4me3 enrichment in promoter regions around the transcriptional start sites, and gene expression of ICAM1, CCL2 and CXCL8 was consistently increased (p < 0.05). KEGG pathway analysis suggested that differential peak-related genes were markedly associated with autoimmune thyroid disease< 0.05).
Conclusions: This first investigation of genome-wide H3K4me3 distribution in thyroid follicular cells suggested that genes associated with autoimmune thyroiditis showed differential H3K4me3 enrichment, which was partly related to gene expression. Global H3K4me3 changes and increased MLL1 expression were found in thyroid tissues from HT patients.
Keywords: ChIP-seq; H3K4me3; Hashimoto’s thyroiditis; chemokine; epigenetics; histone methylation.
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