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Molecular and Cellular Biology, July 2003, p. 4814-4825, Vol. 23, No. 14
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.14.4814-4825.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Sum1 and Ndt80 Proteins Compete for Binding to Middle Sporulation Element Sequences That Control Meiotic Gene Expression

Michael Pierce,1,{dagger} Kirsten R. Benjamin,2 Sherwin P. Montano,3 Millie M. Georgiadis,3 Edward Winter,4 and Andrew K. Vershon1*

Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854,1 Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94143,2 Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202,3 Department of Biochemistry and Molecular Pharmacology, Thomas Jefferson University, Philadelphia, Pennsylvania 191074

Received 28 June 2002/ Returned for modification 26 August 2002/ Accepted 25 April 2003

A key transition in meiosis is the exit from prophase and entry into the nuclear divisions, which in the yeast Saccharomyces cerevisiae depends upon induction of the middle sporulation genes. Ndt80 is the primary transcriptional activator of the middle sporulation genes and binds to a DNA sequence element termed the middle sporulation element (MSE). Sum1 is a transcriptional repressor that binds to MSEs and represses middle sporulation genes during mitosis and early sporulation. We demonstrate that Sum1 and Ndt80 have overlapping yet distinct sequence requirements for binding to and acting at variant MSEs. Whole-genome expression analysis identified a subset of middle sporulation genes that was derepressed in a sum1 mutant. A comparison of the MSEs in the Sum1-repressible promoters and MSEs from other middle sporulation genes revealed that there are distinct classes of MSEs. We show that Sum1 and Ndt80 compete for binding to MSEs and that small changes in the sequence of an MSE can yield large differences in which protein is bound. Our results provide a mechanism for differentially regulating the expression of middle sporulation genes through the competition between the Sum1 repressor and the Ndt80 activator.

* Corresponding author. Mailing address: Waksman Institute, 190 Frelinghuysen Rd., Piscataway, NJ 08854-8020. Phone: (732) 445-2905. Fax: (732) 445-5735. E-mail: vershon{at}waksman.rutgers.edu.

{dagger} Present address: Lewis-Thomas Laboratories, Princeton University, Princeton, N.J.

Molecular and Cellular Biology, July 2003, p. 4814-4825, Vol. 23, No. 14
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.14.4814-4825.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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