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

Author

Listed:
  • Julia R. Pon

    (Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency)

  • Jackson Wong

    (Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency)

  • Saeed Saberi

    (Centre for High-Throughput Biology, University of British Columbia)

  • Olivia Alder

    (Terry Fox Laboratory, BC Cancer Agency)

  • Michelle Moksa

    (Centre for High-Throughput Biology, University of British Columbia)

  • S. -W. Grace Cheng

    (Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency)

  • Gregg B. Morin

    (Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency
    University of British Columbia)

  • Pamela A. Hoodless

    (Terry Fox Laboratory, BC Cancer Agency
    University of British Columbia)

  • Martin Hirst

    (Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency
    Centre for High-Throughput Biology, University of British Columbia)

  • Marco A. Marra

    (Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency
    University of British Columbia)

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.

Suggested Citation

  • Julia R. Pon & Jackson Wong & Saeed Saberi & Olivia Alder & Michelle Moksa & S. -W. Grace Cheng & Gregg B. Morin & Pamela A. Hoodless & Martin Hirst & Marco A. Marra, 2015. "MEF2B mutations in non-Hodgkin lymphoma dysregulate cell migration by decreasing MEF2B target gene activation," Nature Communications, Nature, vol. 6(1), pages 1-15, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8953
    DOI: 10.1038/ncomms8953
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    Cited by:

    1. Chuanjiang Yu & Qiong Shen & Antony B. Holmes & Tongwei Mo & Anna Tosato & Rajesh Kumar Soni & Clarissa Corinaldesi & Sanjay Koul & Laura Pasqualucci & Shafinaz Hussein & Farhad Forouhar & Riccardo Da, 2024. "MEF2B C-terminal mutations enhance transcriptional activity and stability to drive B cell lymphomagenesis," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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