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Molecular and Cellular Biology, January 2009, p. 266-280, Vol. 29, No. 1
0270-7306/09/$08.00+0     doi:10.1128/MCB.00315-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The STAGA Subunit ADA2b Is an Important Regulator of Human GCN5 Catalysis{triangledown} ,{dagger}

Armin M. Gamper, Jaehoon Kim, and Robert G. Roeder*

Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, New York 10021

Received 25 February 2008/ Returned for modification 10 April 2008/ Accepted 10 October 2008

Human STAGA is a multisubunit transcriptional coactivator containing the histone acetyltransferase GCN5L. Previous studies of the related yeast SAGA complex have shown that the yeast Gcn5, Ada2, and Ada3 components form a heterotrimer that is important for the enzymatic function of SAGA. Here, we report that ADA2a and ADA2b, two human homologues of yeast Ada2, each have the ability to form a heterotrimer with ADA3 and GCN5L but that only the ADA2b homologue is found in STAGA. By comparing the patterns of acetylation of several substrates, we found context-dependent requirements for ADA2b and ADA3 for the efficient acetylation of histone tails by GCN5. With human proteins, unlike yeast proteins, the acetylation of free core histones by GCN5 is unaffected by ADA2b or ADA3. In contrast, the acetylation of mononucleosomal substrates by GCN5 is enhanced by ADA2b, with no significant additional effect of ADA3, and the efficient acetylation of nucleosomal arrays (chromatin) by GCN5 requires both ADA2b and ADA3. Thus, ADA2b and ADA3 appear to act at two different levels of histone organization within chromatin to facilitate GCN5 function. Interestingly, although ADA2a forms a complex(es) with GCN5 and ADA3 both in vitro and in vivo, ADA2a-containing complexes are unable to acetylate nucleosomal H3. We have also shown the preferential recruitment of ADA2b, relative to ADA2a, to p53-dependent genes. This finding indicates that the previously demonstrated presence and function of GCN5 on these promoters reflect the action of STAGA and that the ADA2a and ADA2b paralogues have nonredundant functional roles.

* Corresponding author. Mailing address: Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10021. Phone: (212) 327-7600. Fax: (212) 327-7949. E-mail: roeder{at}mail.rockefeller.edu

{triangledown} Published ahead of print on 20 October 2008.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, January 2009, p. 266-280, Vol. 29, No. 1
0270-7306/09/$08.00+0     doi:10.1128/MCB.00315-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Jacobson, S., Pillus, L. (2009). The SAGA Subunit Ada2 Functions in Transcriptional Silencing. Mol. Cell. Biol. 29: 6033-6045 [Abstract] [Full Text]  


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