A Persistence Detector for Metabolic Network Rewiring in an Animal [preprint]
AuthorsBulcha, Jote T.
Giese, Gabrielle E.
Walker, Melissa D.
Holdorf, Amy D.
Yilmaz, L. Safak
Brewster, Robert C
Walhout, Albertha J. M.
UMass Chan AffiliationsGraduate School of Biomedical Sciences
Department of Microbiology and Physiological Systems
Program in Molecular Medicine
Program in Systems Biology
gene regulatory network
Amino Acids, Peptides, and Proteins
Cellular and Molecular Physiology
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AbstractPersistence 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.
bioRxiv 382507; doi: https://doi.org/10.1101/382507. Link to preprint on bioRxiv service.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/29372
RightsThe copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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.
Except where otherwise noted, this item's license is described as The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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.