Program in Systems Biology; Department of Microbiology and Physiological Systems; Program in Molecular Medicine; Graduate School of Biomedical Sciences
Biochemical Phenomena, Metabolism, and Nutrition | Cellular and Molecular Physiology | Genetic Phenomena | Genetics and Genomics | Molecular Biology | Systems Biology
Biological systems must possess mechanisms that prevent inappropriate responses to spurious environmental inputs. Caenorhabditis elegans has two breakdown pathways for the short-chain fatty acid propionate: a canonical, vitamin B12-dependent pathway and a propionate shunt that is used when vitamin B12 levels are low. The shunt pathway is kept off when there is sufficient flux through the canonical pathway, likely to avoid generating shunt-specific toxic intermediates. Here, we discovered a transcriptional regulatory circuit that activates shunt gene expression upon propionate buildup. Nuclear hormone receptor 10 (NHR-10) and NHR-68 function together as a "persistence detector" in a type 1, coherent feed-forward loop with an AND-logic gate to delay shunt activation upon propionate accumulation and to avoid spurious shunt activation in response to a non-sustained pulse of propionate. Together, our findings identify a persistence detector in an animal, which transcriptionally rewires propionate metabolism to maintain homeostasis.
AND-logic gate, C. elegans, feed-forward loop, gene regulatory network, metabolism, persistence detector, propionate, transcription factor, vitamin B12
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Copyright 2018 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
DOI of Published Version
Cell Rep. 2019 Jan 8;26(2):460-468.e4. doi: 10.1016/j.celrep.2018.12.064. Link to article on publisher's site
Bulcha JT, Giese GE, Ali Z, Lee Y, Walker MD, Holdorf AD, Yilmaz LS, Brewster RC, Walhout AJ. (2019). A Persistence Detector for Metabolic Network Rewiring in an Animal. Open Access Publications by UMMS Authors. https://doi.org/10.1016/j.celrep.2018.12.064. Retrieved from https://escholarship.umassmed.edu/oapubs/3746
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