Single-allele nanoscale mapping of regulatory variants.

Single-allele MCCv reveals a neo-CTCF motif creating a gain-of-function mechanism linked to autoimmunity in CD4+ T cells.

• Why it matters: Understanding how noncoding variants influence gene regulation is crucial for deciphering disease mechanisms, especially in immune-related conditions where many variants are noncausal.
• What they did: Researchers developed MCCv to analyze single-allele chromatin structures, phase heterozygous variants, and measure variant effects on chromatin interactions, focusing on 405 cis-regulatory elements in CD4+ T cells.
• The result: They identified a neo-CTCF motif that blocks super-enhancer contacts with SESN3, increasing autoimmunity risk, and demonstrated SESN3’s role in mTOR regulation and autoimmunity in mouse models.