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The Gcn5 bromodomain co-ordinates nucleosome remodelling

Nature volume 404, pages 414–417 (2000)Cite this article

Abstract

The access of transcription factors to eukaryotic promoters often requires modification of their chromatin structure, which is accomplished by the action of two general classes of multiprotein complexes1. One class contains histone acetyltransferases (HATs), such as Gcn5 in the SAGA complex2, which acetylate nucleosomal histones. The second class contains ATPases, such as Swi2 in the Swi/Snf complex3, which provide the energy for nucleosome remodelling. In several promoters these two complexes cooperate but their functional linkage is unknown4,5,6,7,8. A protein module that is present in all nuclear HATs, the bromodomain, could provide such a link9. The recently reported in vitro binding of a HAT bromodomain with acetylated lysines within H3 and H4 amino-terminal peptides10 indicates that this interaction may constitute a targeting step for events that follow histone acetylation. Here we use a suitable promoter to show that bromodomain residues essential for acetyl-lysine binding are not required in vivo for Gcn5-mediated histone acetylation but are fundamental for the subsequent Swi2-dependent nucleosome remodelling and consequent transcriptional activation. We show that the Gcn5 bromodomain stabilizes the Swi/Snf complex on this promoter.

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Figure 1: Expression of the gPHO5–lacZ reporter gene is dependent on the Gcn4 activator, the SAGA complex and the Swi/Snf nucleosome remodelling machine.
Figure 2: Remodelling of the -2 nucleosome in gPHO5 promoter by the Swi/Snf complex requires prior histone acetylation by the SAGA complex.
Figure 3: The Gcn5 bromodomain is required for nucleosome remodelling after histone acetylation.
Figure 4: The Gcn5 bromodomain is required for the stable association of the Swi/Snf complex on the gPHO5 promoter.

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Acknowledgements

We thank D. Thanos for histone antibodies, B. Laurent for the Snf5 antibody, F. Winston for strains, D. Allis for the Gcn5F221A mutant and E. Remboutsika for suggesting the BrTA mutant. This work was supported by a European Union Training and Mobility for Researchers grant.

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Authors and Affiliations

  1. Institute of Molecular Biology and Biotechnology, FORTH, PO Box 1527, Heraklion, Crete, 71110, Greece

    Popi Syntichaki, Irene Topalidou & George Thireos

  2. Department of Biology, University of Crete, Vasilika Vouton, 71409, Heraklio, Crete, Greece

    Popi Syntichaki & Irene Topalidou

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  1. Popi Syntichaki
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Correspondence to George Thireos.

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Syntichaki, P., Topalidou, I. & Thireos, G. The Gcn5 bromodomain co-ordinates nucleosome remodelling. Nature 404, 414–417 (2000). https://doi.org/10.1038/35006136

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