MeCP2’s hidden immune role: how a Rett syndrome protein controls DNA sensing and inflammation

This video summarises the paper “The methyl-CpG-binding protein 2 inhibits cGAS-associated signaling,” published in Nature Communications (2025, PMID: 41203665). Beyond its well-known role in Rett syndrome and gene regulation, MeCP2 is now shown to act as a key brake on the innate immune system. When double-stranded DNA appears in the cytosol, MeCP2 moves out of the nucleus and binds to that DNA, preventing activation of the cGAS–STING pathway, the cell’s alarm system for foreign or damaged DNA. Loss of MeCP2 removes this restraint, triggering chronic inflammation and antiviral responses, and unleashing LINE-1 retroelements that further amplify immune signaling.