Program in Systems Biology; Program in Molecular Medicine; Department of Microbiology and Physiological Systems; Graduate School of Biomedical Sciences
Amino Acids, Peptides, and Proteins | Bacteria | Cellular and Molecular Physiology | Genetic Phenomena | Systems Biology
Persistence detection is a mechanism that ensures a physiological output is only executed when the relevant input is sustained. Gene regulatory network circuits known as coherent type 1 feed forward loops (FFLs) with an AND-logic gate have been proposed to generate persistence detection. In such circuits two transcription factors (TFs) are both required to activate target genes and one of the two TFs activates the other. While numerous FFLs have been identified, examples of actual persistence detectors have only been described for bacteria. Here, we discover a transcriptional persistence detector in Caenorhabditis elegans involving the nuclear hormone receptors nhr-10 and nhr-68, which activates genes comprising a propionate shunt pathway. This shunt is used only when flux through the canonical, vitamin B12-dependent propionate breakdown pathway is perturbed. We propose that the propionate persistence detector functions to preferentially catabolize propionate through the canonical pathway to avoid spurious production of toxic shunt intermediates.
persistence detector, feed-forward loop, AND-logic gate, transcription factor, gene regulatory network, C. elegans, vitamin B12, propionate, metabolism
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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.
DOI of Published Version
bioRxiv 382507; doi: https://doi.org/10.1101/382507. Link to preprint on bioRxiv service.
Bulcha JT, Giese GE, Ali Z, Lee Y, Walker MD, Holdorf AD, Yilmaz LS, Brewster RC, Walhout AJ. (2018). A Persistence Detector for Metabolic Network Rewiring in an Animal [preprint]. UMass Chan Medical School Faculty Publications. https://doi.org/10.1101/382507. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1601
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