Epigenetics and SLE: RFX1 downregulation causes CD11a and CD70 overexpression by altering epigenetic modifications in lupus CD4+ T cells

pVHL/HIF-Regulated CD70 Expression Is Associated with Infiltration of CD27+ Lymphocytes and Increased Serum Levels of Soluble CD27 in Clear Cell Renal Cell Carcinoma

“…It is obvious that in ccRCC, the mechanism of CD70's upregulation is different to that reported in several T-cell affecting diseases, such as systemic lupus erythematosus and systemic sclerosis (35,36) in which hypomethylation of the CD70 promoter contributes to CD70 overexpression. Using the same methylation-specific PCR protocol described by Yu and colleagues (33), no hypomethylation of the CD70 promoter was seen in ccRCC tissues, which strongly expressed CD70 (data not shown).…”

Monocyte Enhancers are Highly Altered in Systemic Lupus Erythematosus

“…This study fills an important knowledge gap by providing critical information on histone modifications in SLE. While DNA methylation has been examined and appears to mold the expression pattern of critical T cell genes in SLE [65,66], there has been only one prior study of histone methylation in SLE which examined total peripheral blood mononuclear cells [67]. Epigenetic changes in cells act in a combinatorial pattern and additional studies will be required to define the critical changes arising in SLE and understand the effects in multiple cell types, the role of the transcription factors in driving these changes and how durable the changes are in this chronic disease.…”

Genetics and Epigenetic in Systemic Lupus Erythematosus

“…Zhao M et al set out a study to uncover mechanisms underlying the hypomethylation and hyperacetylation of genes involved in lupus autoimmunity by investigating the involvement of specific TFs. They assessed the activities of 225 TFs in CD4 + T cells from SLE patients relative to healthy controls using a newly developed screening method (Qiao, 2008), and found that the activity of regulatory factor X 1 (RFX1) is significantly downregulated in SLE CD4 + T cells (Zhao, 2010). Follow-up analyses confirmed the result of Zhao M et al study and further revealed that both the expression and activity of RFX1 protein are reduced in SLE CD4 + T cells.…”

“…Follow-up analyses confirmed the result of Zhao M et al study and further revealed that both the expression and activity of RFX1 protein are reduced in SLE CD4 + T cells. Zhao M et al (Zhao, 2010) also provided evidence indicating that RFX1 recruits the co-repressors HDAC1 and DNMT1 to the promoter region of CD11a and CD70, thus regulating their expression in CD4 + T cells. Taken together, our findings indicate that reduction of RFX1 plays an important role in inducing autoreactivity and autoantibody overstimulation in SLE.…”