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Molecular and Cellular Biology, April 2002, p. 1961-1970, Vol. 22, No. 7
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.7.1961-1970.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The PHD Type Zinc Finger Is an Integral Part of the CBP Acetyltransferase Domain

Eric Kalkhoven,* Hans Teunissen, Ada Houweling, C. Peter Verrijzer, and Alt Zantema

Department of Molecular Cell Biology, MGC Center for Biomedical Genetics, Leiden University Medical Center, 2300 RA Leiden, The Netherlands

Received 23 August 2001/ Returned for modification 27 September 2001/ Accepted 14 December 2001

Histone acetyltransferases (HATs) such as CBP and p300 are regarded as key regulators of RNA polymerase II-mediated transcription, but the critical structural features of their HAT modules remain ill defined. The HAT domains of CBP and p300 are characterized by the presence of a highly conserved putative plant homeodomain (PHD) (C4HC3) type zinc finger, which is part of the functionally uncharacterized cysteine-histidine-rich region 2 (CH2). Here we show that this region conforms to the PHD type zinc finger consensus and that it is essential for in vitro acetylation of core histones and the basal transcription factor TFIIE34 as well as for CBP autoacetylation. PHD finger mutations also reduced the transcriptional activity of the full-length CBP protein when tested on transfected reporter genes. Importantly, similar results were obtained on integrated reporters, which reflect a more natural chromatinized state. Taken together, our results indicate that the PHD finger forms an integral part of the enzymatic core of the HAT domain of CBP.

* Corresponding author. Mailing address: Department of Molecular Cell Biology, Leiden University Medical Center, P.O. Box 9503, 2300 RA Leiden, The Netherlands. Phone: 31-71-5276114. Fax: 31-71-5276284. E-mail: E.Kalkhoven{at}lumc.nl.

Molecular and Cellular Biology, April 2002, p. 1961-1970, Vol. 22, No. 7
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.7.1961-1970.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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