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Molecular and Cellular Biology, May 2003, p. 3392-3404, Vol. 23, No. 10
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.10.3392-3404.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Tax Recruitment of CBP/p300, via the KIX Domain, Reveals a Potent Requirement for Acetyltransferase Activity That Is Chromatin Dependent and Histone Tail Independent

Sara A. Georges,1 Holli A. Giebler,1 Philip A. Cole,2 Karolin Luger,1 Paul J. Laybourn,1 and Jennifer K. Nyborg1*

Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523-1870,1 Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 212052

Received 21 October 2002/ Returned for modification 3 December 2002/ Accepted 4 March 2003

Robust transcription of human T-cell leukemia virus type 1 (HTLV-1) genome requires the viral transactivator Tax. Although Tax has been previously shown to interact with the KIX domain of CBP/p300 in vitro, the precise functional relevance of this interaction remains unclear. Using two distinct approaches to interrupt the physical interaction between Tax and KIX, we find that Tax transactivation from chromatin templates is strongly dependent on CBP/p300 recruitment via the KIX domain. Additionally, we find that the primary functional contribution of CBP/p300 to Tax transactivation resides in the intrinsic acetyltransferase activity of the coactivators. These studies unexpectedly uncover a specific requirement for CBP/p300 acetyltransferase activity on chromatin templates assembled with nucleosomes lacking their amino-terminal tails. Together, these data indicate that the KIX domain of CBP/p300 is essential for targeting the acetyltransferase activity of the coactivator to the Tax-CREB (Tax/CREB) complex. Significantly, these observations reveal the presence of one or more CBP/p300 acetyltransferase targets that function specifically on chromatin templates, are independent of the histone tails, and are critical to Tax transactivation.

* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523-1870. Phone: (970) 491-0420. Fax: (970) 491-0494. E-mail: jnyborg{at}lamar.colostate.edu.

Molecular and Cellular Biology, May 2003, p. 3392-3404, Vol. 23, No. 10
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.10.3392-3404.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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