Publisher Correction: A PRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients

Guéant, Jean‐Louis; Chéry, Céline; Oussalah, Abderrahim; Nadaf, Javad; Coelho, David; Josse, Thomas; Flayac, Justine; Robert, Aurélie; Koscinski, Isabelle; Gastin, Isabelle; Filhine-Trésarrieu, Pierre; Pupavac, Mihaela; Brebner, Alison; Watkins, David; Pastinen, Tomi; Montpetit, Alexandre; Hariri, Fadi; Trégouët, David‐Alexandre; Raby, Benjamin A.; Chung, Wendy K.; Morange, Pierre‐Emmanuel; Froese, D. Sean; Baumgartner, Matthias; Benoist, Jean‐François; Fıçıcıoğlu, Can; Marchand, Virginie; Motorin, Yuri; Bonnemains, C.; Feillet, François; Majewski, Jacek; Rosenblatt, David S.

doi:10.1038/s41467-018-03054-w

Cited by 14 publications

(10 citation statements)

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“…Interestingly, putative HCFC1 binding sites were also identified in the promoters of MTR and ABCD4 ; however, analysis of RNA and protein expression of these genes in fibroblasts showed no difference between HCFC1 patients and controls . In an alternative mechanism, loss of MMACHC expression has been described to be due to mutation of its neighbouring antisense oriented gene PRDX1 , which causes hypermethylation of the promoter and first exon of MMACHC and thereby causes MMACHC silencing . Thus far, no other regulatory mechanisms have been described for proteins proximal to MMACHC in the intracellular Cbl pathway (ie, LMBD1 and ABCD4) or in the mitochondrial pathway (ie, MMAA, MMAB, MMADHC, and MUT).…”

Section: Allosteric Genetic and Epigenetic Regulationmentioning

confidence: 99%

Vitamin B₁₂, folate, and the methionine remethylation cycle—biochemistry, pathways, and regulation

Froese

Fowler

Baumgartner

2019

J of Inher Metab Disea

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283

187

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Vitamin B12 (cobalamin, Cbl) is a nutrient essential to human health. Due to its complex structure and dual cofactor forms, Cbl undergoes a complicated series of absorptive and processing steps before serving as cofactor for the enzymes methylmalonyl‐CoA mutase and methionine synthase. Methylmalonyl‐CoA mutase is required for the catabolism of certain (branched‐chain) amino acids into an anaplerotic substrate in the mitochondrion, and dysfunction of the enzyme itself or in production of its cofactor adenosyl‐Cbl result in an inability to successfully undergo protein catabolism with concomitant mitochondrial energy disruption. Methionine synthase catalyzes the methyl‐Cbl dependent (re)methylation of homocysteine to methionine within the methionine cycle; a reaction required to produce this essential amino acid and generate S‐adenosylmethionine, the most important cellular methyl‐donor. Disruption of methionine synthase has wide‐ranging implications for all methylation‐dependent reactions, including epigenetic modification, but also for the intracellular folate pathway, since methionine synthase uses 5‐methyltetrahydrofolate as a one‐carbon donor. Folate‐bound one‐carbon units are also required for deoxythymidine monophosphate and de novo purine synthesis; therefore, the flow of single carbon units to each of these pathways must be regulated based on cellular needs. This review provides an overview on Cbl metabolism with a brief description of absorption and intracellular metabolic pathways. It also provides a description of folate‐mediated one‐carbon metabolism and its intersection with Cbl at the methionine cycle. Finally, a summary of recent advances in understanding of how both pathways are regulated is presented.

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Section: Allosteric Genetic and Epigenetic Regulationmentioning

confidence: 99%

Vitamin B₁₂, folate, and the methionine remethylation cycle—biochemistry, pathways, and regulation

Froese

Fowler

Baumgartner

2019

J of Inher Metab Disea

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283

187

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“…First, we asked whether some epivariations segregate within the population on specific haplotype backgrounds. 7,9 Using data from 933 individuals from the Women's Health Initiative in whom both methylation and single-nucleotide variation (SNV) data derived from bead arrays were available, we identified 97 epivariations that were present in at least two individuals, and performed association analysis of these with local SNVs. Overall, using a stringent statistical threshold (1% FDR), 68 of the 97 epivariations tested (70%) showed at least one significantly associated SNV (Figure 4, Table S10).…”

Section: Segregation Of Epivariations With Local Sequence Variantsmentioning

confidence: 99%

“…12 Primary epivariations are thought to be caused by stochastic errors in the establishment or maintenance of the epigenome, such as certain types of imprinting anomalies. 13 In contrast, secondary epivariations occur as a result of an underlying change in local DNA sequence and include mutations that disrupt regulatory elements 9,10,14 and expansions of CpG-rich tandem repeats. 15 Large hypermethylated expansions of CGG repeats have been identified at a number of folate-sensitive fragile sites in the human genome, 16 including several that are associated with neurodevelopmental anomalies, such as the CGG expansions that occur at FMR1 (MIM: 309550), AFF2 (MIM: 300806), DIP2B (MIM: 611379), and AFF3 (MIM: 601464).…”

Section: Introductionmentioning

confidence: 99%

A Survey of Rare Epigenetic Variation in 23,116 Human Genomes Identifies Disease-Relevant Epivariations and CGG Expansions

Garg

Jadhav

Rodriguez

et al. 2020

The American Journal of Human Genetics

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There is growing recognition that epivariations, most often recognized as promoter hypermethylation events that lead to gene silencing, are associated with a number of human diseases. However, little information exists on the prevalence and distribution of rare epigenetic variation in the human population. In order to address this, we performed a survey of methylation profiles from 23,116 individuals using the Illumina 450k array. Using a robust outlier approach, we identified 4,452 unique autosomal epivariations, including potentially inactivating promoter methylation events at 384 genes linked to human disease. For example, we observed promoter hypermethylation of BRCA1 and LDLR at population frequencies of $1 in 3,000 and $1 in 6,000, respectively, suggesting that epivariations may underlie a fraction of human disease which would be missed by purely sequence-based approaches. Using expression data, we confirmed that many epivariations are associated with outlier gene expression. Analysis of variation data and monozygous twin pairs suggests that approximately two-thirds of epivariations segregate in the population secondary to underlying sequence mutations, while one-third are likely sporadic events that occur post-zygotically. We identified 25 loci where rare hypermethylation coincided with the presence of an unstable CGG tandem repeat, validated the presence of CGG expansions at several loci, and identified the putative molecular defect underlying most of the known folate-sensitive fragile sites in the genome. Our study provides a catalog of rare epigenetic changes in the human genome, gives insight into the underlying origins and consequences of epivariations, and identifies many hypermethylated CGG repeat expansions.

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“…Peroxidases (PRDXs) are important antioxidant proteins that form a powerful defense system that maintains redox balance by converting hydrogen peroxide to water [ 60 ]. PRDX1 belongs to the PRDX family and is a 23-kDa stress-induced macrophage redox protein that has multiple functions, including managing hydrogen peroxide-mediated oxidative stress in vitro and in vivo, and is a potential target for breast cancer treatment [ 61 – 63 ]. Recently, it was shown that PRDX1 can reduce ROS and inhibit apoptosis induced by the MAPK signaling pathway [ 64 , 65 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Chinese wolfberry and Astragalus extract on the antioxidant capacity of Tibetan pig liver

Hao

Huo

et al. 2021

PLoS ONE

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The objective of this study is to determine the effect of Chinese wolfberry (Lycium barbarum) and Astragalus (Astragalus membranaceus) extract (WAE) on the antioxidant capacity of Tibetan pig liver, and discussed the regulatory effect of WAE on the liver antioxidant mechanism. Twelve healthy 120-day-old Tibetan black pigs (35±2 kg) were divided randomly into two groups. The WAE group was fed a basal diet supplemented with 1% WAE for 90 days. The control group was fed the same diet, but without the WAE. We found that liver superoxide dismutase 1 (SOD1) activity (P<0.05), total antioxidative capacity (T-AOC) (P<0.05), and catalase (CAT) activity (P<0.01) significantly increased in the WAE group compared with the control group; malondialdehyde (MDA) content decreased, but this was not significant (P >0.05). Transcriptome sequencing analysis detected 106 differentially expressed genes (DEGs) related to oxidative stress. GO enrichment analysis showed these DEGs were involved in the positive regulation of reactive oxygen metabolism and biosynthesis, process regulation, and regulation of the oxidative stress response. KEGG Pathway enrichment analysis showed they were enriched in the PI3K-Akt, AMPK, Rap1, and peroxisome signaling pathways. The expression levels of key peroxisome biosynthesis genes (e.g., PEX3 and PEX11B) and key antioxidant genes (e.g., CAT and SOD1) were significantly higher in the WAE group than in the control group. The PRDX1 and PRDX5 content also was significantly higher in the WAE group. This study showed that the WAE regulated the antioxidant and anti-stress ability of Tibetan pig liver through a “peroxisome antioxidant-oxidant stress” signaling pathway.

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Publisher Correction: A PRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients

Cited by 14 publications

References 0 publications

Vitamin B₁₂, folate, and the methionine remethylation cycle—biochemistry, pathways, and regulation

Vitamin B₁₂, folate, and the methionine remethylation cycle—biochemistry, pathways, and regulation

A Survey of Rare Epigenetic Variation in 23,116 Human Genomes Identifies Disease-Relevant Epivariations and CGG Expansions

Effects of Chinese wolfberry and Astragalus extract on the antioxidant capacity of Tibetan pig liver

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Publisher Correction: A PRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients

Cited by 14 publications

References 0 publications

Vitamin B12, folate, and the methionine remethylation cycle—biochemistry, pathways, and regulation

Vitamin B12, folate, and the methionine remethylation cycle—biochemistry, pathways, and regulation

A Survey of Rare Epigenetic Variation in 23,116 Human Genomes Identifies Disease-Relevant Epivariations and CGG Expansions

Effects of Chinese wolfberry and Astragalus extract on the antioxidant capacity of Tibetan pig liver

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Product

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Vitamin B₁₂, folate, and the methionine remethylation cycle—biochemistry, pathways, and regulation

Vitamin B₁₂, folate, and the methionine remethylation cycle—biochemistry, pathways, and regulation