RESEARCH ARTICLE Drosophila SWR1 and NuA4 complexes are defined by DOMINO isoforms Alessandro Scacchetti1, Tamas Schauer2, Alexander Reim3, Zivkos Apostolou1, Aline Campos Sparr1, Silke Krause1, Patrick Heun4, Michael Wierer3, Peter B Becker1* 1Molecular Biology Division, Biomedical Center, Ludwig-Maximilians-University, Munich, Germany; 2Bioinformatics Unit, Biomedical Center, Ludwig-Maximilians- University, Munich, Germany; 3Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Munich, Germany; 4Wellcome Trust Centre for Cell Biology and Institute of Cell Biology, School of Biological Sciences, The University of Edinburgh, Edinburgh, United Kingdom Abstract Histone acetylation and deposition of H2A.Z variant are integral aspects of active transcription. In Drosophila, the single DOMINO chromatin regulator complex is thought to combine both activities via an unknown mechanism. Here we show that alternative isoforms of the DOMINO nucleosome remodeling ATPase, DOM-A and DOM-B, directly specify two distinct multi- subunit complexes. Both complexes are necessary for transcriptional regulation but through different mechanisms. The DOM-B complex incorporates H2A.V (the fly ortholog of H2A.Z) genome-wide in an ATP-dependent manner, like the yeast SWR1 complex. The DOM-A complex, instead, functions as an ATP-independent histone acetyltransferase complex similar to the yeast NuA4, targeting lysine 12 of histone H4. Our work provides an instructive example of how different evolutionary strategies lead to similar functional separation. In yeast and humans, nucleosome remodeling and histone acetyltransferase complexes originate from gene duplication and paralog specification. Drosophila generates the same diversity by alternative splicing of a single gene. *For correspondence:
[email protected] Introduction Competing interests: The Nucleosomes, the fundamental units of chromatin, are inherently stable and organized in polymeric authors declare that no fibers of variable compactness (Baldi et al., 2018; Erdel and Rippe, 2018).