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Molecular and Cellular Biology, March 2009, p. 1176-1188, Vol. 29, No. 5
0270-7306/09/$08.00+0     doi:10.1128/MCB.01599-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Double-Histone-Acetyltransferase Complex ATAC Is Essential for Mammalian Development{triangledown}

Sebastián Guelman,1 Kenji Kozuka,1 Yifan Mao,1 Victoria Pham,2 Mark J. Solloway,3 John Wang,1 Jiansheng Wu,2 Jennie R. Lill,2 and Jiping Zha1*

Department of Pathology, Genentech Inc., South San Francisco, California,1 Department of Protein Chemistry, Genentech Inc., South San Francisco, California,2 Department of Molecular Biology, Genentech Inc., South San Francisco, California3

Received 12 October 2008/ Returned for modification 3 November 2008/ Accepted 9 December 2008

Acetylation of the histone tails, catalyzed by histone acetyltransferases (HATs), is a well-studied process that contributes to transcriptionally active chromatin states. Here we report the characterization of a novel mammalian HAT complex, which contains the two acetyltransferases GCN5 and ATAC2 as well as other proteins linked to chromatin metabolism. This multisubunit complex has a similar but distinct subunit composition to that of the Drosophila ADA2A-containing complex (ATAC). Recombinant ATAC2 has a weak HAT activity directed to histone H4. Moreover, depletion of ATAC2 results in the disassembly of the complex, indicating that ATAC2 not only carries out an enzymatic function but also plays an architectural role in the stability of mammalian ATAC. By targeted disruption of the Atac2 locus in mice, we demonstrate for the first time the essential role of the ATAC complex in mammalian development, histone acetylation, cell cycle progression, and prevention of apoptosis during embryogenesis.


* Corresponding author. Mailing address: Department of Pathology, Genentech Inc., 1 DNA Way MS 72B, South San Francisco, CA 94080. Phone: (650) 225-4947. Fax: (650) 225-8989. E-mail: zha.jiping{at}gene.com

{triangledown} Published ahead of print on 22 December 2008.


Molecular and Cellular Biology, March 2009, p. 1176-1188, Vol. 29, No. 5
0270-7306/09/$08.00+0     doi:10.1128/MCB.01599-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.