The N-terminal domain of TET1 promotes the formation of dense chromatin regions refractory to transcription.


Journal

Chromosoma
ISSN: 1432-0886
Titre abrégé: Chromosoma
Pays: Austria
ID NLM: 2985138R

Informations de publication

Date de publication:
06 2022
Historique:
received: 09 08 2021
accepted: 31 01 2022
revised: 24 01 2022
pubmed: 3 3 2022
medline: 11 5 2022
entrez: 2 3 2022
Statut: ppublish

Résumé

TET (ten-eleven translocation) enzymes initiate active cytosine demethylation via the oxidation of 5-methylcytosine. TET1 is composed of a C-terminal domain, which bears the catalytic activity of the enzyme, and a N-terminal region that is less well characterized except for the CXXC domain responsible for the targeting to CpG islands. While cytosine demethylation induced by TET1 promotes transcription, this protein also interacts with chromatin-regulating factors that rather silence this process, the coordination between these two opposite functions of TET1 being unclear. In the present work, we uncover a new function of the N-terminal part of the TET1 protein in the regulation of the chromatin architecture. This domain of the protein promotes the establishment of a compact chromatin architecture displaying reduced exchange rate of core histones and partial dissociation of the histone linker. This chromatin reorganization process, which does not rely on the CXXC domain, is associated with a global shutdown of transcription and an increase in heterochromatin-associated histone epigenetic marks. Based on these findings, we propose that the dense chromatin organization generated by the N-terminal domain of TET1 could contribute to restraining the transcription enhancement induced by the DNA demethylation activity of this enzyme.

Identifiants

pubmed: 35235010
doi: 10.1007/s00412-022-00769-0
pii: 10.1007/s00412-022-00769-0
doi:

Substances chimiques

Chromatin 0
Histones 0
Proto-Oncogene Proteins 0
5-Methylcytosine 6R795CQT4H
Cytosine 8J337D1HZY
Mixed Function Oxygenases EC 1.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

47-58

Informations de copyright

© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

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Auteurs

Audrey Lejart (A)

Univ Rennes, CNRS, IGDR (Institut de Génétique et Développement de Rennes) - UMR 6290, BIOSIT (Biologie, Santé, Innovation Technologique de Rennes) - UMS 3480, US 018, 35000, Rennes, France.

Siham Zentout (S)

Univ Rennes, CNRS, IGDR (Institut de Génétique et Développement de Rennes) - UMR 6290, BIOSIT (Biologie, Santé, Innovation Technologique de Rennes) - UMS 3480, US 018, 35000, Rennes, France.

Catherine Chapuis (C)

Univ Rennes, CNRS, IGDR (Institut de Génétique et Développement de Rennes) - UMR 6290, BIOSIT (Biologie, Santé, Innovation Technologique de Rennes) - UMS 3480, US 018, 35000, Rennes, France.

Ostiane D'Augustin (O)

Univ Rennes, CNRS, IGDR (Institut de Génétique et Développement de Rennes) - UMR 6290, BIOSIT (Biologie, Santé, Innovation Technologique de Rennes) - UMS 3480, US 018, 35000, Rennes, France.
Institut de Biologie François Jacob, Institute of Cellular and Molecular Radiobiology, Université Paris-Saclay, Université de Paris, CEA, 92265, Fontenay-aux-Roses, France.

Rebecca Smith (R)

Univ Rennes, CNRS, IGDR (Institut de Génétique et Développement de Rennes) - UMR 6290, BIOSIT (Biologie, Santé, Innovation Technologique de Rennes) - UMS 3480, US 018, 35000, Rennes, France.

Gilles Salbert (G)

Univ Rennes, CNRS, IGDR (Institut de Génétique et Développement de Rennes) - UMR 6290, BIOSIT (Biologie, Santé, Innovation Technologique de Rennes) - UMS 3480, US 018, 35000, Rennes, France. gilles.salbert@univ-rennes1.fr.

Sébastien Huet (S)

Univ Rennes, CNRS, IGDR (Institut de Génétique et Développement de Rennes) - UMR 6290, BIOSIT (Biologie, Santé, Innovation Technologique de Rennes) - UMS 3480, US 018, 35000, Rennes, France. sebastien.huet@univ-rennes1.fr.
Institut Universitaire de France, Paris, France. sebastien.huet@univ-rennes1.fr.

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