Human mutations affect the epigenetic/bookmarking function of HNF1B

Jonathan Lerner 1 Alessia Bagattin 1 Francisco Verdeguer 1 Serge Garbay 1 Tristan Felix 1 Laurence Heidet 2 Marco Pontoglio 1, *
* Auteur correspondant
1 UM3 (UMR 8104 / U1016) - Institut Cochin
2 Service de néphrologie pédiatrique [CHU Necker]
Abstract : Bookmarking factors are transcriptional regulators involved in the mitotic transmission of epigenetic information via their ability to remain associated with mitotic chromatin. The mechanisms through which bookmarking factors bind to mitotic chromatin remain poorly understood. HNF1␤ is a bookmarking transcription factor that is frequently mutated in patients suffering from renal multicystic dysplasia and diabetes. Here, we show that HNF1␤ bookmark-ing activity is impaired by naturally occurring mutations found in patients. Interestingly, this defect in HNF1␤ mitotic chromatin association is rescued by an abrupt decrease in temperature. The rapid re-localization to mitotic chromatin is reversible and driven by a specific switch in DNA-binding ability of HNF1␤ mutants. Furthermore, we demonstrate that importin-␤ is involved in the maintenance of the mi-totic retention of HNF1␤, suggesting a functional link between the nuclear import system and the mi-totic localization/translocation of bookmarking factors. Altogether, our studies have disclosed novel aspects on the mechanisms and the genetic programs that account for the mitotic association of HNF1␤, a bookmarking factor that plays crucial roles in the epigenetic transmission of information through the cell cycle.
Type de document :
Article dans une revue
Nucleic Acids Research, Oxford University Press, 2016, [Epub ahead of print]. 〈10.1093/nar/gkw467〉
Liste complète des métadonnées

Littérature citée [39 références]  Voir  Masquer  Télécharger
http://www.hal.inserm.fr/inserm-01361850
Contributeur : Mireille Bos <>
Soumis le : mercredi 7 septembre 2016 - 16:03:31
Dernière modification le : mercredi 29 août 2018 - 01:10:30
Document(s) archivé(s) le : jeudi 8 décembre 2016 - 13:30:55

Fichier

Nucl. Acids Res.-2016-Lerner-n...
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

Collections

UNIV-PARIS5 | USPC

Citation

Jonathan Lerner, Alessia Bagattin, Francisco Verdeguer, Serge Garbay, Tristan Felix, et al.. Human mutations affect the epigenetic/bookmarking function of HNF1B. Nucleic Acids Research, Oxford University Press, 2016, [Epub ahead of print]. 〈10.1093/nar/gkw467〉. 〈inserm-01361850〉

Exporter

BibTeX TEI DC DCterms EndNote

Partager

Métriques

Consultations de la notice

75

Téléchargements de fichiers

102

Contact

support.ccsd.cnrs.fr
hal.support@ccsd.cnrs.fr
Logo CCSD