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PPARγ-induced PARylation promotes local DNA demethylation by production of 5-hydroxymethylcytosine

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  • Katsunori Fujiki

    (Graduate School of Arts and Sciences, The University of Tokyo
    Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo)

  • Akihiro Shinoda

    (Graduate School of Agricultural and Life Sciences, The University of Tokyo)

  • Fumi Kano

    (Graduate School of Arts and Sciences, The University of Tokyo)

  • Ryuichiro Sato

    (Graduate School of Agricultural and Life Sciences, The University of Tokyo)

  • Katsuhiko Shirahige

    (Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo)

  • Masayuki Murata

    (Graduate School of Arts and Sciences, The University of Tokyo)

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.

Suggested Citation

  • Katsunori Fujiki & Akihiro Shinoda & Fumi Kano & Ryuichiro Sato & Katsuhiko Shirahige & Masayuki Murata, 2013. "PPARγ-induced PARylation promotes local DNA demethylation by production of 5-hydroxymethylcytosine," Nature Communications, Nature, vol. 4(1), pages 1-8, October.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3262
    DOI: 10.1038/ncomms3262
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