New chromatin mapping method links autoimmune risk variant to SESN3 gene
The MCCv platform maps chromatin structure on single alleles, letting researchers pinpoint noncoding variants that influence disease genes. In a 2026 study led by Hamley and colleagues, the team examined 405 cis-regulatory elements associated with immune-mediated inflammatory disease in CD4 + T cells. They found a single variant that creates a neo-CTCF motif, which blocks super-enhancer contacts with the SESN3 promoter and heightens autoimmunity risk. SESN3 functions as a tryptophan sensor that regulates the mammalian target of rapamycin. Mouse experiments confirmed this role.
The finding gives geneticists a way to link noncoding variants to autoimmune risk, and the work was done in cells and mouse models rather than human patients.
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