title: Overexpression of histone demethylase Fbxl10 leads to enhanced migration in mouse embryonic fibroblasts.
abstract: Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing, immune responses and invasive tumors all require the orchestrated movement of cells to specific locations. Histone demethylase proteins alter transcription by regulating the chromatin state at specific gene loci. FBXL10 is a conserved and ubiquitously expressed member of the JmjC domain-containing histone demethylase family and is implicated in the demethylation of H3K4me3 and H3K36me2 and thereby removing active chromatin marks. However, the physiological role of FBXL10 in vivo remains largely unknown. Therefore, we established an inducible gain of function model to analyze the role of Fbxl10 and compared wild-type with Fbxl10 overexpressing mouse embryonic fibroblasts (MEFs). Our study shows that overexpression of Fbxl10 in MEFs doesn't influence the proliferation capability but leads to an enhanced migration capacity in comparison to wild-type MEFs. Transcriptome and ChIP-seq experiments demonstrated that Fbxl10 binds to genes involved in migration like Areg, Mdk, Lmnb1, Thbs1, Mgp and Cxcl12. Taken together, our results strongly suggest that Fbxl10 plays a critical role in migration by binding to the promoter region of migration-associated genes and thereby might influences cell behaviour to a possibly more aggressive phenotype.
authors.affiliation: Institute of Pathology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Rohde
authors.affiliation: Institute of Pathology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Sievers
authors.affiliation: Institute of Pathology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Janzer
authors.affiliation: Urologische Klinik/Frauenklinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Breisacherstrasse 66, 79106 Freiburg, Germany.
authors.forename: Dominica
authors.initials: D
authors.lastname: Willmann
authors.affiliation: Department of Developmental Pathology, Institute of Pathology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Egert
authors.affiliation: Department of Developmental Pathology, Institute of Pathology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Hubert
authors.initials: H
authors.lastname: Schorle
authors.affiliation: Urologische Klinik/Frauenklinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Breisacherstrasse 66, 79106 Freiburg, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Schüle
authors.affiliation: Institute of Pathology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany. Electronic address: Jutta.Kirfel@ukb.uni-bonn.de.
authors.forename: Jutta
authors.initials: J
authors.lastname: Kirfel
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D004318:Doxycycline / Q000494:pharmacology; D004622:Embryo, Mammalian / Q000166:cytology*; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D020869:Gene Expression Profiling; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D034741:RNA, Small Interfering / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics; D019076:Transgenes
chemical_list: D044783:F-Box Proteins; D034741:RNA, Small Interfering; D056484:Jumonji Domain-Containing Histone Demethylases; C524747:Kdm2b protein, mouse; D004318:Doxycycline
keywords: Fbxl10; Histone demethylases; Migration; Mouse embryonic fibroblasts