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ATAC is a double histone acetyltransferase complex that stimulates nucleosome sliding

Abstract

The Ada2a-containing (ATAC) complex is an essential Drosophila melanogaster histone acetyltransferase (HAT) complex that contains the transcriptional cofactors Gcn5 (KAT2), Ada3, Ada2a, Atac1 and Hcf. We have analyzed the complex by MudPIT (multidimensional protein identification technology) and found eight previously unidentified subunits. These include the WD40 repeat protein WDS, the PHD and HAT domain protein CG10414 (herein renamed Atac2/KAT14), the YEATS family member D12, the histone fold proteins CHRAC14 and NC2β, CG30390, CG32343 (Atac3) and CG10238. The presence of CG10414 (Atac2) suggests that it acts as a second acetyltransferase enzyme in ATAC in addition to Gcn5. Indeed, recombinant Atac2 displays HAT activity in vitro with a preference for acetylating histone H4, and mutation of Atac2 abrogated H4 lysine 16 acetylation in D. melanogaster embryos. Furthermore, although ATAC does not show nucleosome-remodeling activity itself, it stimulates nucleosome sliding by the ISWI, SWI–SNF and RSC complexes.

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Figure 1: Identification of subunits of the ATAC complex.
Figure 2: Reciprocal purifications of ATAC subunits.
Figure 3: HAT activity of Atac2.
Figure 4: Molecular analysis of D. melanogaster Atac2 mutant embryos.
Figure 5: Acetylation of H4K16 is reduced in atac2[RB]e03046 mutant embryos.
Figure 6: ATAC facilitates nucleosome sliding catalyzed by ISWI and SWI–SNF.

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Acknowledgements

We thank R. Mantovani and M. Hammel for advice on protein structures, K. Wagner for technical assistance, and C. Tomomori-Sato and S. Sato for advice on Flag purification. This research was supported by the Howard Hughes Medical Institute and the Stowers Institute for Medical Research.

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Correspondence to Jerry L Workman.

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Suganuma, T., Gutiérrez, J., Li, B. et al. ATAC is a double histone acetyltransferase complex that stimulates nucleosome sliding. Nat Struct Mol Biol 15, 364–372 (2008). https://doi.org/10.1038/nsmb.1397

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