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Molecular and Cellular Biology, October 2008, p. 6078-6093, Vol. 28, No. 19
0270-7306/08/$08.00+0     doi:10.1128/MCB.00842-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

A New Coactivator Function for Zac1's C2H2 Zinc Finger DNA-Binding Domain in Selectively Controlling PCAF Activity{triangledown}

Anke Hoffmann and Dietmar Spengler*

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

Received 26 May 2008/ Returned for modification 16 June 2008/ Accepted 18 July 2008

The generally accepted paradigm of transcription by regulated recruitment defines sequence-specific transcription factors and coactivators as separate categories that are distinguished by their abilities to bind DNA autonomously. The C2H2 zinc finger protein Zac1, with an established role in canonical DNA binding, also acts as a coactivator. Commensurate with this function, p73, which is related to p53, is here shown to recruit Zac1, together with the coactivators p300 and PCAF, to the p21Cip1 promoter during the differentiation of embryonic stem cells into neurons. In the absence of autonomous DNA binding, Zac1's zinc fingers stabilize the association of PCAF with p300, suggesting its scaffolding function. Furthermore, Zac1 regulates the affinities of PCAF substrates as well as the catalytic activities of PCAF to induce a selective switch in favor of histone H4 acetylation and thereby the efficient transcription of p21Cip1. These results are consistent with an authentic coactivator function of Zac1's C2H2 zinc finger DNA-binding domain and suggest coactivation by sequence-specific transcription factors as a new facet of transcriptional control.


* Corresponding author. Mailing address: Molecular Neuroendocrinology, Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, D-80804 Munich, Germany. Phone: 49 89 30622559. Fax: 49 89 30622605. E-mail: spengler{at}mpipsykl.mpg.de

{triangledown} Published ahead of print on 28 July 2008.


Molecular and Cellular Biology, October 2008, p. 6078-6093, Vol. 28, No. 19
0270-7306/08/$08.00+0     doi:10.1128/MCB.00842-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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