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• W2026344296 abstract "Recent studies have shown that DNA demethylation goes through the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by Tet proteins. However, it is still unclear how the target regions for demethylation are distinguished within their genomic context. Here we show that the nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) has the ability to direct local demethylation around its binding sites, the PPAR response elements (PPREs), during adipocyte differentiation. PPARγ is a key regulator of the differentiation process that forms a PPARγ co-activator complex on PPREs and activates the expression of adipocyte-specific genes. The complex is poly(ADP-ribosyl)ated (PARylated) on PPREs, and Tet proteins catalyse the conversion of 5mC to 5hmC locally by their ability to bind to the PAR polymer, thereby inducing region-specific demethylation. Our study demonstrates that a sequence-dependent transcription factor complex can, through its post-translational modification, serve for Tet proteins as a landmark to identify sites of DNA demethylation. Tet proteins control DNA demethylation, but how the DNA target regions are determined is unclear. Here the authors report that during adipocyte differentiation, PPARγ binds to the PPAR-response element and recruits Tet proteins, thereby inducing local DNA demethylation." @default.
• W2026344296 created "2016-06-24" @default.
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• W2026344296 date "2013-08-05" @default.
• W2026344296 modified "2023-10-05" @default.
• W2026344296 title "PPARγ-induced PARylation promotes local DNA demethylation by production of 5-hydroxymethylcytosine" @default.
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• W2026344296 doi "https://doi.org/10.1038/ncomms3262" @default.
• W2026344296 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23912449" @default.
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