RT Journal
A1 Kuo, Dwight
A1 Licon, Katherine
A1 Bandyopadhyay, Sourav
A1 Chuang, Ryan
A1 Luo, Colin
A1 Catalana, Justin
A1 Ravasi, Timothy
A1 Tan, Kai
A1 Ideker, Trey
T1 Coevolution within a transcriptional network by compensatory trans and cis mutations
JF Genome Research 
JO Genome Research 
YR 2010 
FD December 01 
VO 20 
IS 12 
SP 1672 
OP 1678 
DO 10.1101/gr.111765.110 
UL http://genome.cshlp.org/content/20/12/1672.abstract 
AB Transcriptional networks have been shown to evolve very rapidly, prompting questions as to how such changes arise and are tolerated. Recent comparisons of transcriptional networks across species have implicated variations in the cis-acting DNA sequences near genes as the main cause of divergence. What is less clear is how these changes interact with trans-acting changes occurring elsewhere in the genetic circuit. Here, we report the discovery of a system of compensatory trans and cis mutations in the yeast AP-1 transcriptional network that allows for conserved transcriptional regulation despite continued genetic change. We pinpoint a single species, the fungal pathogen Candida glabrata, in which a trans mutation has occurred very recently in a single AP-1 family member, distinguishing it from its Saccharomyces ortholog. Comparison of chromatin immunoprecipitation profiles between Candida and Saccharomyces shows that, despite their different DNA-binding domains, the AP-1 orthologs regulate a conserved block of genes. This conservation is enabled by concomitant changes in the cis-regulatory motifs upstream of each gene. Thus, both trans and cis mutations have perturbed the yeast AP-1 regulatory system in such a way as to compensate for one another. This demonstrates an example of “coevolution” between a DNA-binding transcription factor and its cis-regulatory site, reminiscent of the coevolution of protein binding partners.