Drosophila SWR1 and NuA4 complexes are defined by DOMINO isoforms

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.

In Vivo Silencing of Genes Coding for dTip60 Chromatin Remodeling Complex Subunits Affects Polytene Chromosome Organization and Proper Development in Drosophila melanogaster

“…It can be envisaged that the Y chromosome short arm telomeric region where the 7m27 insert is located may be devoid of DOM proteins or may not be under their control. These results confirm and extend the findings showing that the dTip60 complex subunits, beside gene activation, are involved in epigenetic silencing [13,18,[27][28][29][30].…”

“…These results suggest that the tested subunits play crucial roles in eye differentiation. They may be involved in the epigenetic regulation of gene expression during development, as shown for the TIP60, DOM-A, and DOM-B [ 13 , 18 ], and their depletion may, in turn, cause up or down regulation of group of target genes, thus perturbing the genetic program required to achieve proper eye differentiation. This is also in accord with the finding showing that the INO80 remodeler can exert both positive and negative of control of homeotic gene expression in D. melanogaster [ 38 ].…”

“…It is then possible that EAF6, GAS41, and MRG15 may be not relevant, or even not essential, for eye development. Alternatively, it is possible that the composition of D. melanogaster chromatin remodeling complexes considered here (dTip60 or DOM-A.C and DOM-B.C) may differ between in vivo eye cells and cultured cell lines [ 13 ]. The last hypothesis is in accord with findings showing that during cellular differentiation, changes in subunit composition of chromatin remodeling complexes indeed play a critical role in establishing cell-type-specific transcriptional programs [ 39 ].…”

“…Recently, mass-spectrometry analyses carried out in D. melanogaster cell lines provided evidence that two DOMINO isoforms, DOM-A and DOM-B, define two different chromatin remodeling complexes, called DOM-A.C and DOM-B.C, characterized by a different subunit composition [ 13 , 14 ]. Among the subunits that have been assigned to dTip60 complex [ 3 ], nine are shared by both DOM-A.C and DOM-B.C, four, (E(PC), ING3, NIPPED-A, and TIP60) are specific for DOM-A.C, while ACT87E, EAF6 e YETI [ 2 , 10 , 11 , 12 ] were not found in DOM-A.C and DOM-B.C.…”

“…Among the subunits that have been assigned to dTip60 complex [ 3 ], nine are shared by both DOM-A.C and DOM-B.C, four, (E(PC), ING3, NIPPED-A, and TIP60) are specific for DOM-A.C, while ACT87E, EAF6 e YETI [ 2 , 10 , 11 , 12 ] were not found in DOM-A.C and DOM-B.C. Finally, ARP6, not included in the dTip60 complex, was identified as a subunit of DOM-B.C [ 13 , 14 ]. Moreover, DOM-A.C was suggested to be the functional equivalent of the yeast NuA4.C, which acetylates the H4 N-terminus [ 15 ], while DOM-B.C is responsible for H2A.V deposition in an ATP-dependent manner.…”