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Molecular and Cellular Biology, June 2001, p. 3830-3839, Vol. 21, No. 11
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.11.3830-3839.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Poly(dA-dT) Promoter Elements Increase the Equilibrium Accessibility of Nucleosomal DNA Target Sites

J. D. Anderson1 and J. Widom1,2,*

Department of Biochemistry, Molecular Biology, and Cell Biology1 and Department of Chemistry2, Northwestern University, Evanston, Illinois 60208

Received 27 November 2000/Returned for modification 3 January 2001/Accepted 12 March 2001

Polypurine tracts are important elements of eukaryotic promoters. They are believed to somehow destabilize chromatin, but the mechanism of their action is not known. We show that incorporating an A16 element at an end of the nucleosomal DNA and further inward destabilizes histone-DNA interactions by 0.1 ± 0.03 and 0.35 ± 0.04 kcal mol-1, respectively, and is accompanied by 1.5- ± 0.1-fold and 1.7- ± 0.1-fold increases in position-averaged equilibrium accessibility of nucleosomal DNA target sites. These effects are comparable in magnitude to effects of A16 elements that correlate with transcription in vivo, suggesting that our system may capture most of their physiological role. These results point to two distinct but interrelated models for the mechanism of action of polypurine tract promoter elements in vivo. Given a nucleosome positioned over a promoter region, the presence of a polypurine tract in that nucleosome's DNA decreases the stability of the DNA wrapping, increasing the equilibrium accessibility of other DNA target sites buried inside that nucleosome. Alternatively (if nucleosomes are freely mobile), the presence of a polypurine tract provides a free energy bias for the nucleosome to move to alternative locations, thereby changing the equilibrium accessibilities of other nearby DNA target sites.

* Corresponding author. Mailing address: Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, 2153 Sheridan Rd., Evanston, IL 60208-3500. Phone: (847) 467-1887. Fax: (847) 467-1380. E-mail: j-widom{at}northwestern.edu.

Molecular and Cellular Biology, June 2001, p. 3830-3839, Vol. 21, No. 11
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.11.3830-3839.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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