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Divergence of Transcription Factor Binding Sites Across Related Yeast Species
Anthony R. Borneman,1*Tara A. Gianoulis,2Zhengdong D. Zhang,3Haiyuan Yu,3Joel Rozowsky,3Michael R. Seringhaus,3Lu Yong Wang,4Mark Gerstein,2,3,5Michael Snyder1,2,3
Characterization of interspecies differences in gene regulationis crucial for understanding the molecular basis of both phenotypicdiversity and evolution. By means of chromatin immunoprecipitationand DNA microarray analysis, the divergence in the binding sitesof the pseudohyphal regulators Ste12 and Tec1 was determinedin the yeasts Saccharomyces cerevisiae, S. mikatae, and S. bayanusunder pseudohyphal conditions. We have shown that most of thesesites have diverged across these species, far exceeding theinterspecies variation in orthologous genes. A group of Ste12targets was shown to be bound only in S. mikatae and S. bayanusunder pseudohyphal conditions. Many of these genes are targetsof Ste12 during mating in S. cerevisiae, indicating that specializationbetween the two pathways has occurred in this species. Transcriptionfactor binding sites have therefore diverged substantially fasterthan ortholog content. Thus, gene regulation resulting fromtranscription factor binding is likely to be a major cause ofdivergence between related species.
1 Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA. 2 Program in Computational Biology, Yale University, New Haven, CT 06511, USA. 3 Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511, USA. 4 Integrated Data Systems Department, Siemens Corporate Research, Princeton, NJ 08540, USA. 5 Department of Computer Science, Yale University, New Haven, CT 06511, USA.
* Present address: Australian Wine Research Institute, Glen Osmond,Adelaide, SA 5064, Australia.
To whom correspondence should be addressed. E-mail: michael.snyder{at}yale.edu
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