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Nature Communications
Article . 2013 . Peer-reviewed
License: Springer Nature TDM
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PPARγ-induced PARylation promotes local DNA demethylation by production of 5-hydroxymethylcytosine

Authors: Katsunori Fujiki; Akihiro Shinoda; Fumi Kano; Ryuichiro Sato; Katsuhiko Shirahige; Masayuki Murata;

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

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.

Country
Japan
Keywords

Poly Adenosine Diphosphate Ribose, Base Sequence, Molecular Sequence Data, Cell Differentiation, DNA Methylation, Phenanthrenes, Hydroxylation, DNA-Binding Proteins, PPAR gamma, Cytosine, Mice, Enhancer Elements, Genetic, HEK293 Cells, Adipose Tissue, 3T3-L1 Cells, 5-Methylcytosine, Adipocytes, Animals, Humans, Amino Acid Sequence

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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    103
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
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    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
103
Top 10%
Top 10%
Top 10%
gold