Multiple domains of Matɑ1 transcription factor contribute to binding site specificity

Among homologous transcription factors with the same function, DNA-binding specificity can diverge. Matα1 is a high mobility group (HMG) box transcription factor in budding yeast whose Saccharomyces cerevisiae and Candida albicans homologs regulate α-specific genes but bind distinct cis-regulatory sequences. To identify the protein features underlying this divergence, we generated structure-guided chimeras and measured their activity using species-specific reporters. Replacing any of the four Matα1 regions reduced activation of the S. cerevisiae reporter, while all chimeras retained activity on the C. albicans reporter. Thus, all four regions of Matα - not just the HMG box domain - are important for sequence specificity.