The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Non-CpG methylation of the PGC-1α promoter through DNMT3B controls mitochondrial density.
Open accessAbstract
Epigenetic modification through DNA methylation is implicated in metabolic disease. Using whole-genome promoter methylation analysis of skeletal muscle from normal glucose-tolerant and type 2 diabetic subjects, we identified cytosine hypermethylation of peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1 alpha (PGC-1alpha) in diabetic subjects. Methylation levels were negatively correlated with PGC-1alpha mRNA and mitochondrial DNA (mtDNA). Bisulfite sequencing revealed that the highest proportion of cytosine methylation within PGC-1alpha was found within non-CpG nucleotides. Non-CpG methylation was acutely increased in human myotubes by exposure to tumor necrosis factor-alpha (TNF-alpha) or free fatty acids, but not insulin or glucose. Selective silencing of the DNA methyltransferase 3B (DNMT3B), but not DNMT1 or DNMT3A, prevented palmitate-induced non-CpG methylation of PGC-1alpha and decreased mtDNA and PGC-1alpha mRNA. We provide evidence for PGC-1alpha hypermethylation, concomitant with reduced mitochondrial content in type 2 diabetic patients, and link DNMT3B to the acute fatty-acid-induced non-CpG methylation of PGC-1alpha promoter.
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“In turn, PGC-1␣ expression may also be reduced as a consequence of promoter methylation (146) or caused by insulin itself (145), obesity (126), and sustained lipid exposure (126).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [146]
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Cites
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DAVID: Database for Annotation, Visualization, and Integrated Discovery
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Dysfunction of Mitochondria in Human Skeletal Muscle in Type 2 Diabetes
Kelley, D. E., He, J., Menshikova, E. V., & Ritov, V. B. (2002) · Diabetes · doi:10.2337/diabetes.51.10.2944 · Cited by 2,321
Metabolic control through the PGC-1 family of transcription coactivators
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Chromatin modification and epigenetic reprogramming in mammalian development
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Epigenetic inheritance at the agouti locus in the mouse
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Sex differences in human adipose tissues – the biology of pear shape
Karastergiou, K., Smith, S. R., Greenberg, A. S., & Fried, S. K. (2012) · Biology of Sex Differences · doi:10.1186/2042-6410-3-13 · Cited by 1,109
Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle
Barrès, R., Yan, J., Egan, B., Treebak, J. T., Rasmussen, M., Fritz, T., Caidahl, K., Krook, A., O'Gorman, D. J., & Zierath, J. R. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.01.001 · Cited by 965
“Evidence is emerging that epigenetic modifications through DNA methylation contribute to the increased risk and development of metabolic disease by modifying the expression of genes controlling whole body energy and glucose homeostasis (Barrès et al., 2009; Klose and Bird, 2006).”
BackgroundInfluentialSelf-citationEpigenetics in Human Obesity and Type 2 Diabetes
Ling, C., & Rönn, T. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.03.009 · Cited by 1,006
Human body epigenome maps reveal noncanonical DNA methylation variation
Schultz, M. D., He, Y., Whitaker, J. W., Hariharan, M., Mukamel, E. A., Leung, D., Rajagopal, N., Nery, J. R., Urich, M. A., Chen, H., et al. (2015) · Nature · doi:10.1038/nature14465 · Cited by 690
Metadata
- Authors
- Barrès, R., Osler, M. E., Yan, J., Rune, A., Fritz, T., Caidahl, K., Krook, A., & Zierath, J. R.
- Affiliations
- Karolinska University Hospital (SE)
- Corresponding author
- Zierath, Juleen R.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2009-09
- Volume
- 10
- Issue
- 3
- Pages
- 189-198
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W1985280131
- Semantic Scholar
- 4a04e95dbe0297f0a51059b2ab7890362fad1e57
- Cited by
- 602
- References
- 44
- Citations by year
- 2026: 26 · 2025: 16 · 2024: 27 · 2023: 24 · 2022: 26 · 2021: 37 · 2020: 24 · 2019: 35 · 2018: 36 · 2017: 41 · 2016: 50 · 2015: 57 · 2014: 49 · 2013: 43 · 2012: 39
- FWCI
- 14.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1451 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Novo Nordisk UK Research Foundation
- Vetenskapsrådet
- European Commission (LSHM-CT-2004-005272, LSHM-CT-2004-512013 EUGENE2)
- European Research Council
- European Foundation for the Study of Diabetes
- Knut och Alice Wallenbergs Stiftelse
- Glenn Foundation for Medical Research
- Stockholms Läns Landsting
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- PGC-1α, DNMT3B, promoter methylation, mitochondrial density, type 2 diabetes, skeletal muscle, mitochondrial DNA, free fatty acids, palmitate, TNF-α, myotubes, DNA methyltransferases, epigenetic regulation
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, DNA Methyltransferase 3B, Base Sequence, Diabetes Mellitus, Type 2, DNA (Cytosine-5-)-Methyltransferases, DNA, Mitochondrial, Fatty Acids, Heat-Shock Proteins, Humans, Mitochondria, Promoter Regions, Genetic, RNA, Messenger, Transcription Factors, Tumor Necrosis Factor-alpha, CpG Islands, DNA Methylation, Muscle Cells, RNA, Small Interfering
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