Distinct DAXX effector modules separate H3.3 nucleosome assembly from ERV repression.

A conserved basic patch in the DAXX histone-binding domain is required for H3.3 nucleosome assembly at DAXX-bound ERVs, but DAXX-dependent ERV repression persists without H3.3 deposition.

• Why it matters: ERVs threaten genome integrity when expressed, and cells rely on chromatin pathways to silence them; how DAXX recruitment translates into repression is unclear.
• What they did: Using biochemical and genetic assays, the study mapped a DNA-engaging basic patch in DAXX that promotes H3.3 nucleosome assembly in vitro and is needed for H3.3 enrichment at DAXX-bound ERVs in cells.
• The result: DAXX substitutions that block H3.3 deposition still localize to ERVs and preserve repression, whereas disrupting the DAXX C-terminal SUMO-interacting motif impairs ERV repression and SUMO-dependent effector engagement, including MORC3 recruitment.

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