ИСТИНА

The Interleukin 2 receptor alpha (IL2RA) chain is required for the development of regulatory lymphocytes which play a central role in the control of autoimmunity. Not surprisingly, numerous single nucleotide polymorphisms (SNPs) that are associated with various autoimmune diseases have been located in the human IL2RA locus. One of these SNPs, rs61839660, overlaps with a number of characteristic epigenetic signatures of regulatory elements. In particular, this SNP maps to a putative binding site of Mef2c (myocyte-specific enhancer factor 2C) that is highly expressed in bone marrow and in peripheral B-cells. Using pulldown assay, we demonstrated rs61839660-dependent Mef2c binding to the corresponding DNA probe from IL2RA locus, with stronger binding to the common variant of the polymorphism. Currently, we are testing the ability of the sequences containing various SNPs from the first intron of IL2RA gene to regulate the activity of the IL2RA promoter, depending on the variant of the polymorphism. We aim to determine which transcription factors bind to SNPs that can directly influence IL2RA expression.