title: MEF2B mutations in non-Hodgkin lymphoma dysregulate cell migration by decreasing MEF2B target gene activation.
abstract: Myocyte enhancer factor 2B (MEF2B) is a transcription factor with mutation hotspots at K4, Y69 and D83 in diffuse large B-cell lymphoma (DLBCL). To provide insight into the regulatory network of MEF2B, in this study, we analyse global gene expression and DNA-binding patterns. We find that candidate MEF2B direct target genes include RHOB, RHOD, CDH13, ITGA5 and CAV1, and that indirect target genes of MEF2B include MYC, TGFB1, CARD11, MEF2C, NDRG1 and FN1. MEF2B overexpression increases HEK293A cell migration and epithelial-mesenchymal transition, and decreases DLBCL cell chemotaxis. K4E, Y69H and D83V MEF2B mutations decrease the capacity of MEF2B to activate transcription and decrease its' effects on cell migration. The K4E and D83V mutations decrease MEF2B DNA binding. In conclusion, our map of the MEF2B regulome connects MEF2B to drivers of oncogenesis.
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, Canada V5Z 1L3.
authors.forename: Julia R
authors.initials: JR
authors.lastname: Pon
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, Canada V5Z 1L3.
authors.forename: Jackson
authors.initials: J
authors.lastname: Wong
authors.affiliation: Department of Microbiology and Immunology, Centre for High-Throughput Biology, University of British Columbia, Vancouver, Canada V6T 1Z4.
authors.forename: Saeed
authors.initials: S
authors.lastname: Saberi
authors.affiliation: Terry Fox Laboratory, BC Cancer Agency, Vancouver, Canada V5Z 1L3.
authors.forename: Olivia
authors.initials: O
authors.lastname: Alder
authors.affiliation: Department of Microbiology and Immunology, Centre for High-Throughput Biology, University of British Columbia, Vancouver, Canada V6T 1Z4.
authors.forename: Michelle
authors.initials: M
authors.lastname: Moksa
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, Canada V5Z 1L3.
authors.forename: S-W
authors.initials: SW
authors.lastname: Grace Cheng
authors.affiliation: 1] Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, Canada V5Z 1L3 [2] Department of Medical Genetics, University of British Columbia, Vancouver, Canada V6T 1Z3.
authors.forename: Gregg B
authors.initials: GB
authors.lastname: Morin
authors.affiliation: 1] Terry Fox Laboratory, BC Cancer Agency, Vancouver, Canada V5Z 1L3 [2] Department of Medical Genetics, University of British Columbia, Vancouver, Canada V6T 1Z3.
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Hoodless
authors.affiliation: 1] Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, Canada V5Z 1L3 [2] Department of Microbiology and Immunology, Centre for High-Throughput Biology, University of British Columbia, Vancouver, Canada V6T 1Z4.
authors.forename: Martin
authors.identifier: 0000000191369054
authors.initials: M
authors.lastname: Hirst
authors.affiliation: 1] Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, Canada V5Z 1L3 [2] Department of Medical Genetics, University of British Columbia, Vancouver, Canada V6T 1Z3.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Marra
mesh_terms: D001665:Binding Sites; D002465:Cell Movement; D002470:Cell Survival; D002633:Chemotaxis; D004268:DNA-Binding Proteins / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000378:metabolism; D064326:MEF2 Transcription Factors / Q000235:genetics; D009154:Mutation; D011401:Promoter Regions, Genetic; D051560:Proto-Oncogene Proteins c-bcl-6; D015533:Transcriptional Activation; D059467:Transcriptome
chemical_list: C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D064326:MEF2 Transcription Factors; C578038:MEF2B protein, human; D051560:Proto-Oncogene Proteins c-bcl-6