UMMS Affiliation

Program in Systems Biology; Department of Microbiology and Physiological Systems; Program in Molecular Medicine; Graduate School of Biomedical Sciences

Publication Date

2019-01-08

Document Type

Article

Disciplines

Biochemical Phenomena, Metabolism, and Nutrition | Cellular and Molecular Physiology | Genetic Phenomena | Genetics and Genomics | Molecular Biology | Systems Biology

Abstract

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.

Keywords

AND-logic gate, C. elegans, feed-forward loop, gene regulatory network, metabolism, persistence detector, propionate, transcription factor, vitamin B12

Rights and Permissions

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

10.1016/j.celrep.2018.12.064

Source

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

Journal/Book/Conference Title

Cell reports

Related Resources

Link to Article in PubMed

PubMed ID

30625328

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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