UMMS Affiliation
Program in Systems Biology; Program in Molecular Medicine; Graduate School of Biomedical Sciences
Publication Date
2020-10-05
Document Type
Article
Disciplines
Amino Acids, Peptides, and Proteins | Biochemistry | Cellular and Molecular Physiology | Computational Biology | Hormones, Hormone Substitutes, and Hormone Antagonists | Systems Biology
Abstract
Vitamin B12 is an essential micronutrient that functions in two metabolic pathways: the canonical propionate breakdown pathway and the methionine/S-adenosylmethionine (Met/SAM) cycle. In Caenorhabditis elegans, low vitamin B12, or genetic perturbation of the canonical propionate breakdown pathway results in propionate accumulation and the transcriptional activation of a propionate shunt pathway. This propionate-dependent mechanism requires nhr-10 and is referred to as 'B12-mechanism-I'. Here, we report that vitamin B12 represses the expression of Met/SAM cycle genes by a propionate-independent mechanism we refer to as 'B12-mechanism-II'. This mechanism is activated by perturbations in the Met/SAM cycle, genetically or due to low dietary vitamin B12. B12-mechanism-II requires nhr-114 to activate Met/SAM cycle gene expression, the vitamin B12 transporter, pmp-5, and adjust influx and efflux of the cycle by activating msra-1 and repressing cbs-1, respectively. Taken together, Met/SAM cycle activity is sensed and transcriptionally adjusted to be in a tight metabolic regime.
Keywords
C. elegans, chromosomes, computational biology, gene expression, metabolism, methionine/sam cycle, nuclear hormone receptor, systems biology, transcription factors, vitamin B12
Rights and Permissions
Copyright © 2020, Giese et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
DOI of Published Version
10.7554/eLife.60259
Source
Giese GE, Walker MD, Ponomarova O, Zhang H, Li X, Minevich G, Walhout AJ. Caenorhabditis elegans methionine/S-adenosylmethionine cycle activity is sensed and adjusted by a nuclear hormone receptor. Elife. 2020 Oct 5;9:e60259. doi: 10.7554/eLife.60259. PMID: 33016879; PMCID: PMC7561351. Link to article on publisher's site
Journal/Book/Conference Title
eLife
Related Resources
PubMed ID
33016879
Repository Citation
Giese GE, Walker MD, Ponomarova O, Zhang H, Li X, Minevich G, Walhout AJ. (2020). Caenorhabditis elegans methionine/S-adenosylmethionine cycle activity is sensed and adjusted by a nuclear hormone receptor. Open Access Publications by UMMS Authors. https://doi.org/10.7554/eLife.60259. Retrieved from https://escholarship.umassmed.edu/oapubs/4401
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Amino Acids, Peptides, and Proteins Commons, Biochemistry Commons, Cellular and Molecular Physiology Commons, Computational Biology Commons, Hormones, Hormone Substitutes, and Hormone Antagonists Commons, Systems Biology Commons