National Academy of Sciences, Proceedings of the National Academy of Sciences, 34(115), 2018
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Significance Transcription factors have been intensively examined to decipher how they regulate cellular decisions, but there are few in-depth studies of these factors across traits, environments, and genetic backgrounds. Here, we analyze the Saccharomyces cerevisiae Ste12 protein, a transcription factor essential for both mating and invasion in many fungal species. Generating thousands of variants in the Ste12 DNA-binding domain, we scored each variant for its activity in promoting both mating and invasion. We found altered DNA-binding patterns of exceptional variants that result in yeast that lose their mating efficiency, but gain increased competence in invasion. This surprising malleability in transcription factor function has implications for understanding the evolution of pathogenicity in fungi.