Flightless-I governs cell fate by recruiting the SUMO isopeptidase SENP3 to distinct HOX genes

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 t
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.
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Metadaten
Author:Arnab Nayak, Anja Reck, Christian Morsczeck, Stefan Müller
URN:urn:nbn:de:hebis:30:3-456260
DOI:http://dx.doi.org/10.1186/s13072-017-0122-8
ISSN:1756-8935
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=28344658
Parent Title (English):Epigenetics & chromatin
Publisher:BioMed Central
Place of publication:London
Document Type:Article
Language:English
Year of Completion:2017
Date of first Publication:2017/03/23
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/02/06
Tag:Chromatin; Flightless-I; HOX gene; MLL1/2; Mesenchymal stem cells; SILAC-based proteomics; Sumoylation
Volume:10
Issue:Art. 15
Pagenumber:13
First Page:1
Last Page:13
Note:
© The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
HeBIS PPN:426725409
Institutes:Biochemie und Chemie
Dewey Decimal Classification:540 Chemie und zugeordnete Wissenschaften
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0

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