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Molecular and Cellular Biology, October 1998, p. 5818-5827, Vol. 18, No. 10
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Requirements for Chromatin Modulation and Transcription Activation by the Pho4 Acidic Activation Domain

P. C. McAndrew,1 J. Svaren,2,dagger S. R. Martin,3 W. Hörz,2 and C. R. Goding1,*

Eukaryotic Transcription Laboratory, Marie Curie Research Institute, The Chart, Oxted, Surrey RH8 0TL,1 and National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA,3 United Kingdom, and Institut für Physiologische Chemie, Universität München, D-80336 Munich, Germany2

Received 17 December 1997/Returned for modification 5 February 1998/Accepted 28 July 1998

Perhaps the best characterized example of an activator-induced chromatin transition is found in the activation of the Saccharomyces cerevisiae acid phosphatase gene PHO5 by the basic helix-loop-helix (bHLH) transcription factor Pho4. Transcription activation of the PHO5 promoter by Pho4 is accompanied by the remodeling of four positioned nucleosomes which is dependent on the Pho4 activation domain but independent of transcription initiation. Whether the requirements for transcription activation through the TATA sequence are different from those necessary for the chromatin transition remains a major outstanding question. In an attempt to understand better the ability of Pho4 to activate transcription and to remodel chromatin, we have initiated a detailed characterization of the Pho4 activation domain. Using both deletion and point mutational analysis, we have defined residues between positions 75 and 99 as being both essential and sufficient to mediate transcription activation. Significantly, there is a marked concordance between the ability of mutations in the Pho4 activation domain to induce chromatin opening and transcription activation. Interestingly, the requirements for transcription activation within the Pho4 activation domain differ significantly if fused to a heterologous bHLH-leucine zipper DNA-binding domain. The implications for transcription activation by Pho4 are discussed.

* Corresponding author. Mailing address: Eukaryotic Transcription Laboratory, Marie Curie Research Institute, The Chart, Oxted, Surrey RH8 0TL, United Kingdom. Phone: 44 1883 722306. Fax: 44 1883 730426. E-mail: c.goding{at}mcri.ac.uk.

dagger Present address: Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110-1093.

Molecular and Cellular Biology, October 1998, p. 5818-5827, Vol. 18, No. 10
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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