MacroH2A1 and H3K27me3 target cGAS to facultative heterochromatin to restrain innate immune activation
The DNA sensor cGAS is largely sequestered on chromatin in an inactive form, but how this state is regulated remains unclear. We show that cGAS preferentially binds nucleosomes containing the histone variant macroH2A1 (mH2A1) marked by H3K27me3 and H3K9me3. Cryo-EM reveals that cGAS selectively engages the mH2A1/H2B acidic patch within heterotypic nucleosomes. Depleting mH2A1.1 or blocking…
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