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• W2989552607 endingPage "e1007497" @default.
• W2989552607 startingPage "e1007497" @default.
• W2989552607 abstract "Organisms must ensure that expression of genes is directed to the appropriate tissues at the correct times, while simultaneously ensuring that these gene regulatory systems are robust to perturbation. This idea is captured by a mathematical concept called r-robustness, which says that a system is robust to a perturbation in up to r − 1 randomly chosen parameters. r-robustness implies that the biological system has a small number of sensitive parameters and that this number can be used as a robustness measure. In this work we use this idea to investigate the robustness of gene regulation using a sequence level model of the Drosophila melanogaster gene even-skipped. We consider robustness with respect to mutations of the enhancer sequence and with respect to changes of the transcription factor concentrations. We find that gene regulation is r-robust with respect to mutations in the enhancer sequence and identify a number of sensitive nucleotides. In both natural and in silico predicted enhancers, the number of nucleotides that are sensitive to mutation correlates negatively with the length of the sequence, meaning that longer sequences are more robust. The exact degree of robustness obtained is dependent not only on DNA sequence, but also on the local concentration of regulatory factors. We find that gene regulation can be remarkably sensitive to changes in transcription factor concentrations at the boundaries of expression features, while it is robust to perturbation elsewhere." @default.
• W2989552607 created "2019-11-22" @default.
• W2989552607 creator A5039576473 @default.
• W2989552607 creator A5039670277 @default.
• W2989552607 creator A5041358651 @default.
• W2989552607 date "2019-11-15" @default.
• W2989552607 modified "2023-10-18" @default.
• W2989552607 title "An in silico analysis of robust but fragile gene regulation links enhancer length to robustness" @default.
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• W2989552607 doi "https://doi.org/10.1371/journal.pcbi.1007497" @default.
• W2989552607 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6881076" @default.
• W2989552607 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31730659" @default.
• W2989552607 hasPublicationYear "2019" @default.
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