PLX035468

GSE110676: Germinal Center B cell transcriptional profiles in Mef2b mouse models

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

The MEF2B transcription factor is recurrently mutated in germinal-center (GC)-derived B-cell lymphomas, but its role in normal and neoplastic GC development is unknown. Here we identify MEF2B transcriptional targets in GC, which indicate its control of cell proliferation, apoptosis, GC confinement and differentiation. Consistently, Mef2b deletion reduces GC formation in mice. The most common tumor-associated MEF2B mutant (MEF2BD83V) is hypomorphic, but escapes binding and negative regulation by Cabin1 and HDACs. Mef2bD83V expression leads to GC enlargement and GC-derived tumors in 25% of the animals. This phenotype becomes fully penetrant in combination with BCL2 de-regulation, an event commonly associated with MEF2B mutations in human lymphoma. These results identify MEF2B as a critical GC regulator, and as a dominant oncogene in lymphomagenesis. SOURCE: Riccardo Dalla-Favera (rd10@columbia.edu) - Columbia University