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Originally published In Press as doi:10.1074/jbc.M101385200 on May 30, 2001

J. Biol. Chem., Vol. 276, Issue 30, 28179-28184, July 27, 2001
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The Histone Acetyltransferase, hGCN5, Interacts with and Acetylates the HIV Transactivator, Tat*

Edwige ColDagger , Cécile CaronDagger , Daphné Seigneurin-Berny§, Jocelyne GraciaDagger , Alain FavierDagger , and Saadi Khochbin§

From the Dagger  Laboratoire de Biologie du Stress Oxydant, Faculté de Pharmacie, Domaine de la Merci, 38700 La Tronche Cedex and the § Laboratoire de Biologie Moléculaire et Cellulaire de la Différenciation, INSERM U309, Institut Albert Bonniot, Faculté de Médecine, Domaine de la Merci, 38706 La Tronche Cedex, France

Factor acetyltransferase activity associated with several histone acetyltransferases plays a key role in the control of transcription. Here we report that hGCN5, a well known histone acetyltransferase, specifically interacts with and acetylates the human immunodeficiency virus type 1 (HIV-1) transactivator protein, Tat. The interaction between Tat and hGCN5 is direct and involves the acetyltransferase and the bromodomain regions of hGCN5, as well as a limited region of Tat encompassing the cysteine-rich domain of the protein. Tat lysines 50 and 51, target of acetylation by p300/CBP, were also found to be acetylated by hGCN5. The acetylation of these two lysines by p300/CBP has been recently shown to stimulate Tat transcriptional activity and accordingly, we have found that hGCN5 can considerably enhance Tat-dependent transcription of the HIV-1 long terminal repeat. These data highlight the importance of the acetylation of lysines 50 and 51 in the function of Tat, since different histone acetyltransferases involved in distinct signaling pathways, GCN5 and p300/CBP, converge to acetylate Tat on the same site.


* This work was supported by Sidaction Contract 991249/23026-01-00/AO10-1 (to S. K.) and Contract 000013/30041-03-00/AO10-1 (to C. C.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed. E-mail: khochbin@ujf-grenoble.fr.


Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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