Knocking down Set1 by Set1-siRNA in SLE CD4+ T cells contributed to up-regulation of DNA methylation and DNMT3a at the CREMα promoter, and overproduction of IL-2, while Set1 and H3K4me3 enrichments within the region were attenuated, and CREMα and IL-17A abundances were suppressed. This evidence concerns the gene CD4 and systemic lupus erythematosus.