On the mechanistic nature of epistasis in a canonical cis-regulatory element.

ABSTRACT: Understanding the relation between genotype and phenotype remains a major challenge. The difficulty of predicting individual mutation effects, and particularly the interactions between them, has prevented the development of a comprehensive theory that links genotypic changes to their phenotypic effects. We show that a general thermodynamic framework for gene regulation, based on a biophysical understanding of protein-DNA binding, accurately predicts the sign of epistasis in a canonical cis-regulatory element consisting of overlapping RNA polymerase and repressor binding sites. Sign and magnitude of individual mutation effects are sufficient to predict the sign of epistasis and its environmental dependence. Thus, the thermodynamic model offers the correct null prediction for epistasis betwe

SUBMITTER: Lagator M 

PROVIDER: S-EPMC5481185 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature