Genome-wide Analysis Of Histone H3 Lysine 4 Trimethylation In Peripheral Blood Mononuclear Cells Of Systemic Lupus Erythematosus Patients

Objects:To analyze the histone H3 lysien4 trimethylation changes in peripheral blood mononuclear cells in systemic lupus erythematosus(SLE) patients and to investigate the pathogenesis of SLE.Methods:SLE patients were classified as active and inactive disease by the SLE disease activity index(SLEDAI).RA patients and healthy subjects were chosed as control.PBMCs was isolated by density gradient centrifugation from 10 active SLE patients,7 inactive SLE patients,8 rheumatoid arthritis(RA) and 8 healthy volunteers. ChIP-quantitative PCR was used to validate the microarray results.Expression analysis by qRT-PCR revealed correlations between mRNA and H3K4me3 levels. Methyl-DNA immunoprecipitation-quantitative PCR(MeDIP-qPCR) was used to investigate the DNA methylation status.Results:413(137 increased and 276 decreased H3K4me3) and 393 probes(112 increased and 281 decreased H3K4me3 )displayed significant H3K4me3 differences were found in active and inactive SLE comparied with healthy subjects,respectively. 270 probes with significant H3K4me3 differences were identified in between active and inactive SLE patients.Among these probes,151 displayed increased H3K4me3 and 119 showed decreased H3K4me3.236(169 increased and 67 decreased H3K4me3) and 202 probes(139 increased and 63 decreased H3K4me3) displayed significant H3K4me3 differences were found in active and inactive SLE comparied with RA patients respectively.364 probes(66 increased and 298 decreased H3K4me3) with significant H3K4me3 differences were also identified in between RA patients and healthy subjects.The results of ChIP-qPCR were coincided well with microarray. H3K4me3 variations in SLE patients compared with healthy controls have an positive correlation with mRNA expression levels.We also found an inverse relationship between H3K4me3 and promoter DNA methylation in SLE patients.Conclusion:There are significant differences in H3K4me3 profiling between SLE and healthy subjects.H3K4me3 alterations are involved in the pathogenesis of SLE. These novel candidate genes may be become potential biomarkers or future therapeutic targets.The ChiP-chip technology will help further reveal SLE molecular mechanisms and discover new therapeutic targets.