This was considered reasonable, as the changes were still highly significant

3 are altered in key relevant candidate genes, such as PTPN22 and LRP1B, in PBMCs in SLE patients. The CD70 gene is 7 highly expressed in SLE T cells and is involved in the synthesis of autoreactive antibodies. Active histone markers, such as H3ac and H3K4me2, in the CD70 promoter were shown to be significantly increased in SLE CD4+ T cells and to positively correlate with the disease activity. Both TNF gene expression and histone acetylation at the TNF locus were shown to be enhanced in monocytes of SLE patients. Protein phosphatase 2A is a serine/threonine phosphatase and highly expressed in SLE T cells. Overexpression of PP2A in murine T cells causes glomerulonephritis in an IL-17-dependent manner. IL-17 is produced by T helper 17 cells that are implicated in autoimmune diseases. PP2A enhances IL-17 gene expression through H3ac. A genome-wide analysis showed PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19841886 that H4ac is significantly altered in monocytes of SLE patients. Sixty-three percent of genes with increased H4ac are associated with the regulation by interferon regulatory factor 1, suggesting that interferon contributes to the pathogenesis of SLE. Hematopoietic progenitor kinase 1 represses the T cell-mediated immune response. H3K27me3 is enriched in the HPK1 promoter and HPK1 expression is reduced in SLE CD4+ T cells. The downregulation of HPK1 results in accelerated T cell proliferation and the production of IFN and immunoglobulins. The binding of JMJD3 that demethylates H3K27 is decreased, while the binding of EZH2 that methylates H3K27 is not altered in the HPK1 promoter in SLE CD4+ T cells. Global hypoacetylation of the histones H3 and H4 has been detected in CD4+ T cells of active SLE patients. The level of H3ac is negatively correlated with the disease activity. Global hypomethylation of H3K9 was observed in CD4+ T cells of both active and inactive SLE patients, whereas global H3K4 methylation levels were not altered in SLE CD4+ T cells. The gene expression of histone-modifying enzymes was shown to be aberrant in SLE CD4+ T cells. SIRT1 gene expression is significantly increased, while CBP, p300, HDAC2, HDAC7, SUV39H2, and EZH2 gene expression is significantly decreased in CD4+ T cells of active SLE patients. Regulatory factor Xbox 1, which interacts with HDAC1 and SUV39H1, is downregulated in SLE. Therefore, H3ac is increased and H3K9me3 is decreased in the promoters of CD11a and CD70 in SLE CD4+ T cells, resulting in CD11a and CD70 overexpression and autoimmune responses. H3K18 deacetylation by HDAC1 results in a silencing of the IL-2 gene in SLE T cells. TSA significantly downregulates CD154 and IL-10 gene expression and upregulates IFN gene expression in SLE T cells. 4.3. SSc. The inhibition of H3K27me3 by 3-deazaneplanocin stimulates the release of collagen, induces the profibrotic transcription factor fos-related antigen 2, and PTK/ZK exacerbates the fibrosis induced by transforming growth factor in cultured SSc fibroblasts. JMJD3 was reported to be highly expressed and the level of H3K27me3 is decreased in SSc CD4+ T cells. As a result, specific genes, such as CD40L, CD70, and CD11a, are activated in SSc, leading to the autoimmune response. Global histone H4 hyperacetylation and histone H3K9 hypomethylation have been reported in SSc B cells 8. JHDM2A expression is increased, whereas HDAC2, HDAC7, and SUV39H2 expression is decreased in SSc B cells. Global H4ac is negatively correlated with HDAC2 expression. The former was shown to be positively correlated with the diseas