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

Link to Article in PubMed

PubMed ID

33016879

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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