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 Previous Article

Molecular and Cellular Biology, July 2006, p. 5544-5557, Vol. 26, No. 14
0270-7306/06/$08.00+0     doi:10.1128/MCB.02270-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Multitasking C2H2 Zinc Fingers Link Zac DNA Binding to Coordinated Regulation of p300-Histone Acetyltransferase Activity

Anke Hoffmann, Thomas Barz, and Dietmar Spengler*

Molecular Neuroendocrinology, Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, D-80804 Munich, Germany

Received 28 November 2005/ Returned for modification 6 January 2006/ Accepted 27 April 2006

Zac is a C2H2 zinc finger protein that regulates apoptosis and cell cycle arrest through DNA binding and transactivation. The coactivator proteins p300/CBP enhance transactivation through their histone acetyltransferase (HAT) activity by modulating chromatin structure. Here, we show that p300 increases Zac transactivation in a strictly HAT-dependent manner. Whereas the classic recruitment model proposes that coactivation simply depends on the capacity of the activator to recruit the coactivator, we demonstrate that coordinated binding of Zac zinc fingers and C terminus to p300 regulates HAT function by increasing histone and acetyl coenzyme A affinities and catalytic activity. This concerted regulation of HAT function is mediated via the KIX and CH3 domains of p300 in an interdependent manner. Interestingly, Zac zinc fingers 6 and 7 simultaneously play key roles in DNA binding and p300 regulation. Our findings demonstrate, for the first time, that C2H2 zinc fingers can link DNA binding to HAT signaling and suggest a dynamic role for DNA-binding proteins in the enzymatic control of transcription.


* Corresponding author. Mailing address: Molecular Neuroendocrinology, Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, D-80804 Munich, Germany. Phone: 49 89 30622 559. Fax: 49 89 30622 605. E-mail: spengler{at}mpipsykl.mpg.de.


Molecular and Cellular Biology, July 2006, p. 5544-5557, Vol. 26, No. 14
0270-7306/06/$08.00+0     doi:10.1128/MCB.02270-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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