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Mutational sources of trans-regulatory variation affecting gene expression in Saccharomyces cerevisiae.

Fabien Duveau, Petra Vande Zande, Brian P Metzger, Crisandra J Diaz, Elizabeth A Walker, Stephen Tryban, Mohammad A Siddiq, Bing Yang, and Patricia J Wittkopp (2021)

Elife, 10.

Heritable variation in a gene's expression arises from mutations impacting cis- andtrans-acting components of its regulatory network. Here, we investigate howtrans-regulatory mutations are distributed within the genome and within a generegulatory network by identifying and characterizing 69 mutations withtrans-regulatory effects on expression of the same focal gene in Saccharomycescerevisiae. Relative to 1766 mutations without effects on expression of this focalgene, we found that these trans-regulatory mutations were enriched in codingsequences of transcription factors previously predicted to regulate expression ofthe focal gene. However, over 90% of the trans-regulatory mutations identifiedmapped to other types of genes involved in diverse biological processes includingchromatin state, metabolism, and signal transduction. These data show how geneticchanges in diverse types of genes can impact a gene's expression in trans, revealingproperties of trans-regulatory mutations that provide the raw material fortrans-regulatory variation segregating within natural populations.

 
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