title: Increased expressions of DNA methyltransferases contribute to CD70 promoter hypomethylation and over expression of CD70 in ITP.
abstract: CD70 (TNFSF7), as a methylation susceptive immune gene, was hypomethylated in some autoimmune diseases. To investigate the status of CD70 methylation and the expressions of genes that regulated methylation in immune thrombocytopenia (ITP) patients, the expressions of CD70 mRNA and protein in CD4(+) T cells from ITP and controls were measured respectively by real-time PCR and flow cytometry. Methylation specific high resolution melting (MS-HRM) technology was applied to detect CD70 promoter methylation indices. Transcription levels of DNA methyltransferases (DNMTs), methylated CpG binding protein 2 (MBD2) were measured. The results showed that CD70, DNMTs and MBD2 was over expressed and methylation indices of CD70 promoter in CD4(+) T cells from ITP patients were lower than that from healthy controls. The transcription levels of CD70 showed significantly inverse correlation with methylation indices in ITP patients but significantly positive correlation with that of DNMTs. We concluded that DNMTs functioned as demethylases as MBD2, while increased DNMTs and MBD2 may cause demethylation and over expression of CD70 in CD4(+) T cells, potentially contributing to the pathogenesis of ITP.
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Zeping
authors.initials: Z
authors.lastname: Zhou
authors.forename: Hongmei
authors.initials: H
authors.lastname: Wang
authors.forename: Hu
authors.initials: H
authors.lastname: Zhou
authors.forename: Donglei
authors.initials: D
authors.lastname: Zhang
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Li
authors.forename: Aiping
authors.initials: A
authors.lastname: Qi
authors.forename: Renchi
authors.initials: R
authors.lastname: Yang
mesh_terms: D000328:Adult; D001327:Autoimmune Diseases / Q000235:genetics / Q000378:metabolism; D053282:CD27 Ligand / Q000235:genetics* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D008297:Male; D008780:Methyltransferases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013921:Thrombocytopenia / Q000235:genetics / Q000276:immunology*; D015534:Trans-Activators; D014158:Transcription, Genetic
chemical_list: D053282:CD27 Ligand; C409062:CXXC1 protein, human; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D015254:DNA Modification Methylases; D008780:Methyltransferases