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The metazoan ATAC and SAGA coactivator HAT complexes regulate different sets of inducible target genes

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Abstract

Histone acetyl transferases (HATs) play a crucial role in eukaryotes by regulating chromatin architecture and locus-specific transcription. The GCN5 HAT was identified as a subunit of the SAGA (Spt-Ada-Gcn5-Acetyltransferase) multiprotein complex. Vertebrate cells express a second HAT, PCAF, that is 73% identical to GCN5. Here, we report the characterization of the mammalian ATAC (Ada-Two-A-Containing) complexes containing either GCN5 or PCAF in a mutually exclusive manner. In vitro ATAC complexes acetylate lysine 14 of histone H3. Moreover, ATAC- or SAGA-specific knock-down experiments suggest that both ATAC and SAGA are involved in the acetylation of histone H3K9 and K14 residues. Despite their catalytic similarities, SAGA and ATAC execute their coactivator functions on distinct sets of inducible target genes. Interestingly, ATAC strongly influences the global phosphorylation level of histone H3S10, suggesting that in mammalian cells a cross-talk exists linking ATAC function to H3S10 phosphorylation.

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Acknowledgments

We are grateful to W. Herr, B. Malecova and T. Oelgeschläger for reagents, to R. and J. Conaway for sharing unpublished results, to R. Schneider, K. Kamieniarz, J. Bonnet and G. Lang for suggestions and help with the HAT assays, to the IGBMC core facilities, and to D. Devys, B. Malecova and T. Pankotai for critically reading the manuscript. Z.N. was supported by a fellowship from the European Community grant (HPRN-CT-00504228) and by a fellowship from the Fondation pour la Recherche Médicale (FRM). A.R. and A.K. were supported by fellowships of the Alsace Region. This work was supported by funds from CNRS, INSERM, Université de Strasbourg, the FRM, and European Community (HPRN-CT 00504228, STREP LSHG-CT-2004-502950 and EUTRACC LSHG-CT-2007-037445) and INCA (2008-UBICAN) grants.

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Authors and Affiliations

  1. Department of Functional Genomics, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR 7104, INSERM U 964, Université de Strasbourg, BP 10142, 67404, Illkirch Cedex, CU de Strasbourg, France

    Zita Nagy, Anne Riss, Arnaud Krebs, Meritxell Orpinell & Làszlò Tora

  2. Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan

    Sally Fujiyama & Shigeaki Kato

  3. Department of Molecular Biology, NCMLS 274, Radboud University Nijmegen, PO Box 9101, 6500 HB, Nijmegen, The Netherlands

    Pascal Jansen, Adrian Cohen & Henk G. Stunnenberg

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  1. Zita Nagy
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  2. Anne Riss
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  10. Làszlò Tora
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Correspondence to Làszlò Tora.

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Z. Nagy and A. Riss contributed equally to this work.

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Nagy, Z., Riss, A., Fujiyama, S. et al. The metazoan ATAC and SAGA coactivator HAT complexes regulate different sets of inducible target genes. Cell. Mol. Life Sci. 67, 611–628 (2010). https://doi.org/10.1007/s00018-009-0199-8

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