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Human mutations affect the epigenetic/bookmarking function of HNF1B

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. HNF1β is a bookmarking...

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Autores principales: Lerner, Jonathan, Bagattin, Alessia, Verdeguer, Francisco, Makinistoglu, Munevver P., Garbay, Serge, Felix, Tristan, Heidet, Laurence, Pontoglio, Marco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5041451/
https://www.ncbi.nlm.nih.gov/pubmed/27229139
http://dx.doi.org/10.1093/nar/gkw467
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author Lerner, Jonathan
Bagattin, Alessia
Verdeguer, Francisco
Makinistoglu, Munevver P.
Garbay, Serge
Felix, Tristan
Heidet, Laurence
Pontoglio, Marco
author_facet Lerner, Jonathan
Bagattin, Alessia
Verdeguer, Francisco
Makinistoglu, Munevver P.
Garbay, Serge
Felix, Tristan
Heidet, Laurence
Pontoglio, Marco
author_sort Lerner, Jonathan
collection PubMed
description 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. HNF1β is a bookmarking transcription factor that is frequently mutated in patients suffering from renal multicystic dysplasia and diabetes. Here, we show that HNF1β bookmarking activity is impaired by naturally occurring mutations found in patients. Interestingly, this defect in HNF1β mitotic chromatin association is rescued by an abrupt decrease in temperature. The rapid relocalization to mitotic chromatin is reversible and driven by a specific switch in DNA-binding ability of HNF1β mutants. Furthermore, we demonstrate that importin-β is involved in the maintenance of the mitotic retention of HNF1β, suggesting a functional link between the nuclear import system and the mitotic 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 HNF1β, a bookmarking factor that plays crucial roles in the epigenetic transmission of information through the cell cycle.
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spelling pubmed-50414512016-09-30 Human mutations affect the epigenetic/bookmarking function of HNF1B Lerner, Jonathan Bagattin, Alessia Verdeguer, Francisco Makinistoglu, Munevver P. Garbay, Serge Felix, Tristan Heidet, Laurence Pontoglio, Marco Nucleic Acids Res Gene regulation, Chromatin and Epigenetics 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. HNF1β is a bookmarking transcription factor that is frequently mutated in patients suffering from renal multicystic dysplasia and diabetes. Here, we show that HNF1β bookmarking activity is impaired by naturally occurring mutations found in patients. Interestingly, this defect in HNF1β mitotic chromatin association is rescued by an abrupt decrease in temperature. The rapid relocalization to mitotic chromatin is reversible and driven by a specific switch in DNA-binding ability of HNF1β mutants. Furthermore, we demonstrate that importin-β is involved in the maintenance of the mitotic retention of HNF1β, suggesting a functional link between the nuclear import system and the mitotic 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 HNF1β, a bookmarking factor that plays crucial roles in the epigenetic transmission of information through the cell cycle. Oxford University Press 2016-09-30 2016-05-26 /pmc/articles/PMC5041451/ /pubmed/27229139 http://dx.doi.org/10.1093/nar/gkw467 Text en © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Gene regulation, Chromatin and Epigenetics
Lerner, Jonathan
Bagattin, Alessia
Verdeguer, Francisco
Makinistoglu, Munevver P.
Garbay, Serge
Felix, Tristan
Heidet, Laurence
Pontoglio, Marco
Human mutations affect the epigenetic/bookmarking function of HNF1B
title Human mutations affect the epigenetic/bookmarking function of HNF1B
title_full Human mutations affect the epigenetic/bookmarking function of HNF1B
title_fullStr Human mutations affect the epigenetic/bookmarking function of HNF1B
title_full_unstemmed Human mutations affect the epigenetic/bookmarking function of HNF1B
title_short Human mutations affect the epigenetic/bookmarking function of HNF1B
title_sort human mutations affect the epigenetic/bookmarking function of hnf1b
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5041451/
https://www.ncbi.nlm.nih.gov/pubmed/27229139
http://dx.doi.org/10.1093/nar/gkw467
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