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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.

MEF2B mutations in non-Hodgkin lymphoma dysregulate cell migration by decreasing MEF2B target gene activation