TY - JOUR TI - Drosophila SWR1 and NuA4 complexes are defined by DOMINO isoforms AU - Scacchetti, Alessandro AU - Schauer, Tamas AU - Reim, Alexander AU - Apostolou, Zivkos AU - Campos Sparr, Aline AU - Krause, Silke AU - Heun, Patrick AU - Wierer, Michael AU - Becker, Peter B A2 - Workman, Jerry L A2 - Struhl, Kevin A2 - Workman, Jerry L A2 - Weake, Vikki VL - 9 PY - 2020 DA - 2020/05/20 SP - e56325 C1 - eLife 2020;9:e56325 DO - 10.7554/eLife.56325 UR - https://doi.org/10.7554/eLife.56325 AB - 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. KW - chromatin KW - transcription KW - histone exchange KW - histone acetylation KW - histone h2a.z KW - nucleosome remodeling JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -