MEF2B mutations in non-Hodgkin lymphoma dysregulate cell migration by decreasing MEF2B target gene activation
| Autor: | Julia R. Pon, Pamela A. Hoodless, Marco A. Marra, Michelle Moksa, Martin Hirst, Jackson Wong, Saeed Saberi, S.-W. Grace Cheng, Olivia Alder, Gregg B. Morin |
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| Rok vydání: | 2014 |
| Předmět: |
Transcriptional Activation
Epithelial-Mesenchymal Transition Cell Survival RHOB General Physics and Astronomy Regulome Biology medicine.disease_cause General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences 0302 clinical medicine Cell Movement medicine Humans MEF2C Promoter Regions Genetic Gene Transcription factor 030304 developmental biology Regulation of gene expression 0303 health sciences Cell chemotaxis Multidisciplinary Binding Sites MEF2 Transcription Factors Chemotaxis General Chemistry DNA-Binding Proteins Gene Expression Regulation Neoplastic HEK293 Cells 030220 oncology & carcinogenesis Mutation Cancer research Proto-Oncogene Proteins c-bcl-6 Lymphoma Large B-Cell Diffuse Carcinogenesis Transcriptome |
| Zdroj: | Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. Mutations in the transcription factor MEF2B are found in diffuse large B-cell lymphoma. In this study, the authors map the DNA-binding sites of the transcription factor in cells in vitro and find that the mutations decrease the ability of MEF2B to activate transcription. |
| Databáze: | OpenAIRE |
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