A strong positive correlation was demonstrated between L1 transcripts and gene products that mediate de novo and constitutive DNA methylation, DNA methyltransferase (DNMT)3B, DNMT1, and methyl CpG binding protein 2 (MeCP2), in both SS MSG and lupus renal tissues.
DNA methylation changes in lupus T cells play a central role in the pathogenesis of lupus, and MeCp-2 (encoded by MECP2) is a master regulator of gene expression and is also known to recruit DNA methyltransferase 1 (DNMT1) during DNA synthesis.
Recent reports describe variable expression of a number of regulatory microRNAs in lupus CD4+ T cells, some of which govern the expression of DNA methyltransferase 1.
Additionally, inhibition of miR-21 and miR-148a expression in CD4+ T cells from patients with lupus could increase DNMT1 expression and attenuate DNA hypomethylation.
We show that decreased ERK pathway signaling in T cells results in decreased expression of DNA methyltransferase 1 and overexpression of the methylation-sensitive genes CD11a and CD70, similar to T cells in human lupus.