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Proc Natl Acad Sci U S A. 2017 Aug 1;114(31):8229-8234. doi: 10.1073/pnas.1702192114. Epub 2017 Jul 17.

Methylcytosine dioxygenase TET3 interacts with thyroid hormone nuclear receptors and stabilizes their association to chromatin.

Author information

1
Shanghai Key Laboratory of Regulatory Biology, The Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
2
Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, CNRS, Ecole Normale Supérieure de Lyon, 69364 Lyon cedex 07, France.
3
Shanghai Key Laboratory of Regulatory Biology, The Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China; karine.gauthier@ens-lyon.fr jmweng@bio.ecnu.edu.cn.
4
Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, CNRS, Ecole Normale Supérieure de Lyon, 69364 Lyon cedex 07, France karine.gauthier@ens-lyon.fr jmweng@bio.ecnu.edu.cn.

Abstract

Thyroid hormone receptors (TRs) are members of the nuclear hormone receptor superfamily that act as ligand-dependent transcription factors. Here we identified the ten-eleven translocation protein 3 (TET3) as a TR interacting protein increasing cell sensitivity to T3. The interaction between TET3 and TRs is independent of TET3 catalytic activity and specifically allows the stabilization of TRs on chromatin. We provide evidence that TET3 is required for TR stability, efficient binding of target genes, and transcriptional activation. Interestingly, the differential ability of different TRα1 mutants to interact with TET3 might explain their differential dominant activity in patients carrying TR germline mutations. So this study evidences a mode of action for TET3 as a nonclassical coregulator of TRs, modulating its stability and access to chromatin, rather than its intrinsic transcriptional activity. This regulatory function might be more general toward nuclear receptors. Indeed, TET3 interacts with different members of the superfamily and also enhances their association to chromatin.

KEYWORDS:

RTH syndrome; chromatin recruitment; methylcytosine dioxygenase TET3; protein stability; thyroid hormone receptor

PMID:
28716910
PMCID:
PMC5547603
DOI:
10.1073/pnas.1702192114
[Indexed for MEDLINE]
Free PMC Article

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