Nayak, Arnab and Reck, Anja and Morsczeck, Christian and Mueller, Stefan (2017) Flightless-I governs cell fate by recruiting the SUMO isopeptidase SENP3 to distinct HOX genes. EPIGENETICS & CHROMATIN, 10: 15. ISSN 1756-8935,
Full text not available from this repository. (Request a copy)Abstract
Background: Despite recent studies on the role of ubiquitin-related SUMO modifier in cell fate decisions, our understanding on precise molecular mechanisms of these processes is limited. Previously, we established that the SUMO isopeptidase SENP3 regulates chromatin assembly of the MLL1/2 histone methyltransferase complex at distinct HOX genes, including the osteogenic master regulator DLX3. A comprehensive mechanism that regulates SENP3 transcriptional function was not understood. Results: Here, we identified flightless-I homolog (FLII), a member of the gelsolin family of actin-remodeling proteins, as a novel regulator of SENP3. We demonstrate that FLII is associated with SENP3 and the MLL1/2 complex. We further show that FLII determines SENP3 recruitment and MLL1/2 complex assembly on the DLX3 gene. Consequently, FLII is indispensible for H3K4 methylation and proper loading of active RNA polymerase II at this gene locus. Most importantly, FLII-mediated SENP3 regulation governs osteogenic differentiation of human mesenchymal stem cells. Conclusion: Altogether, these data reveal a crucial functional interconnection of FLII with the sumoylation machinery that converges on epigenetic regulation and cell fate determination.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HUMAN DENTAL FOLLICLE; EMBRYONIC STEM-CELLS; MIXED LINEAGE LEUKEMIA; OSTEOGENIC DIFFERENTIATION; CHROMATIN-STRUCTURE; BIVALENT PROMOTERS; ESTROGEN-RECEPTOR; PRECURSOR CELLS; GROUP PROTEINS; WOUND REPAIR; Sumoylation; MLL1/2; HOX gene; Mesenchymal stem cells; Flightless-I; Chromatin; SILAC-based proteomics |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Mund-, Kiefer- und Gesichtschirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:00 |
| Last Modified: | 20 Feb 2019 11:34 |
| URI: | https://pred.uni-regensburg.de/id/eprint/204 |
Actions (login required)
 |
View Item |
