Molecular mechanism of residue-specific nucleosome acetylation.

Cryo-EM structures reveal how the MSL complex specifically acetylates H4K16 in nucleosomes during active catalysis in Drosophila.

• Why it matters: Understanding the precise mechanisms of histone acetylation is crucial for insights into transcription regulation and disease, yet the dynamic details of HAT complex function remain unclear.
• What they did: The study used cryo-EM to visualize the Drosophila MSL complex engaged in catalysis, capturing a stable product state and showing how subunits act as a molecular ruler and recognize H3K36 trimethylation.
• The result: Findings demonstrate how the MSL complex achieves residue-specific acetylation, linking enzymatic activity to transcriptionally active gene bodies and providing molecular principles for histone modification regulation.