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10.7554/eLife.25192 http://scihub22266oqcxt.onion/10.7554/eLife.25192 C5481185!5481185!28518057     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       eLife 2017 ; 6 (ä): ä Nephropedia Template TP {{tp|p=28518057|t=2017. On the mechanistic nature of epistasis in a canonical cis-regulatory element |pdf=|usr=}}{{28518057}} gab.com Text On the mechanistic nature of epistasis in a canonical cis-regulatory element JO: eLife http://www.kidney.de/pget.php?&tw=1&pmid=28518057 #FOAvip 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 between mutations across DNA-binding sites. Our results indicate that a predictive theory for the effects of cis-regulatory mutations is possible from first principles, as long as the essential molecular mechanisms and the constraints these impose on a biological system are accounted for.DOI:http://dx.doi.org/10.7554/eLife.25192.001 Twit Text FOAVip On the mechanistic nature of epistasis in a canonical cis-regulatory element ????eLife http://www.kidney.de/pget.php?&tw=1&pmid=28518057 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28518057 #FOAvip English Wikipedia <ref>{{Cite pmid|28518057}}</ref> On the mechanistic nature of epistasis in a canonical cis-regulatory element #MMPMID28518057 Lagator M; Paixão T; Barton NH; Bollback JP; Guet CC eLife 2017[]; 6 (ä): ä PMID28518057show ga 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 between mutations across DNA-binding sites. Our results indicate that a predictive theory for the effects of cis-regulatory mutations is possible from first principles, as long as the essential molecular mechanisms and the constraints these impose on a biological system are accounted for.DOI:http://dx.doi.org/10.7554/eLife.25192.001 äOn the mechanistic nature of epistasis in a canonical cis-regulatory e(epmc).pdf DeepDyve Pubget Overpricing