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Non-CpG methylation...
Non-CpG methylation of the PGC-1alpha promoter through DNMT3B controls mitochondrial density
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Barres, R. (författare)
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- Osler, M. E. (författare)
- Karolinska Institutet
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- Yan, J. (författare)
- Karolinska Institutet
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- Rune, A. (författare)
- Karolinska Institutet
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- Fritz, T. (författare)
- Karolinska Institutet
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- Caidahl, Kenneth, 1949 (författare)
- Karolinska Institutet,Gothenburg University,Göteborgs universitet,Extern,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,External,Institute of Medicine, Department of Molecular and Clinical Medicine
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- Krook, A. (författare)
- Karolinska Institutet
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- Zierath, J. R. (författare)
- Karolinska Institutet
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(creator_code:org_t)
- Elsevier BV, 2009
- 2009
- Engelska.
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 10:3, s. 189-98
- Relaterad länk:
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http://www.cell.com/...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Nyckelord
- Base Sequence
- CpG Islands/genetics
- DNA (Cytosine-5-)-Methyltransferases/*metabolism
- *DNA Methylation
- DNA
- Mitochondrial/metabolism
- Diabetes Mellitus
- Type 2/*genetics/metabolism/pathology
- Fatty Acids/pharmacology
- Heat-Shock Proteins/*genetics/metabolism
- Humans
- Mitochondria/*genetics/metabolism/ultrastructure
- Muscle Cells/metabolism
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
- Promoter Regions
- Genetic
- RNA
- Messenger/metabolism
- RNA
- Small Interfering/metabolism
- Transcription Factors/*genetics/metabolism
- Tumor Necrosis Factor-alpha/pharmacology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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