Caenorhabditis elegans methionine/S-adenosylmethionine cycle activity is sensed and adjusted by a nuclear hormone receptor
UMass Chan Affiliations
Graduate School of Biomedical SciencesProgram in Molecular Medicine
Program in Systems Biology
Document Type
Journal ArticlePublication Date
2020-10-05Keywords
C. eleganschromosomes
computational biology
gene expression
metabolism
methionine/sam cycle
nuclear hormone receptor
systems biology
transcription factors
vitamin B12Amino Acids, Peptides, and ProteinsBiochemistryCellular and Molecular PhysiologyComputational BiologyHormones, Hormone Substitutes, and Hormone AntagonistsSystems Biology
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Show full item recordAbstract
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.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
DOI
10.7554/eLife.60259Permanent Link to this Item
http://hdl.handle.net/20.500.14038/41614PubMed ID
33016879Related Resources
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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.Distribution License
http://creativecommons.org/licenses/by/4.0/Scopus Count
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Except where otherwise noted, this item's license is described as 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.
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