 |
Journal articles
Human mutations affect the epigenetic/bookmarking function of HNF1B
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.
Cited literature [39 references]
https://www.hal.inserm.fr/inserm-01361850
Contributor : Mireille Bos Connect in order to contact the contributor
Submitted on : Wednesday, September 7, 2016 - 4:03:31 PM
Last modification on : Tuesday, October 19, 2021 - 11:57:43 PM
Long-term archiving on: : Thursday, December 8, 2016 - 1:30:55 PM
Contributor : Mireille Bos Connect in order to contact the contributor
Submitted on : Wednesday, September 7, 2016 - 4:03:31 PM
Last modification on : Tuesday, October 19, 2021 - 11:57:43 PM
Long-term archiving on: : Thursday, December 8, 2016 - 1:30:55 PM
File
Nucl. Acids Res.-2016-Lerner-n...
Publisher files allowed on an open archive