A Persistence Detector for Metabolic Network Rewiring in an Animal
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
Program in Molecular Medicine
Department of Microbiology and Physiological Systems
Program in Systems Biology
gene regulatory network
Biochemical Phenomena, Metabolism, and Nutrition
Cellular and Molecular Physiology
Genetics and Genomics
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AbstractBiological 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.
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
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/40946
RightsCopyright 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/).
Except where otherwise noted, this item's license is described as 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/).