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MEF2B Instructs Germinal Center Development and Acts as an Oncogene in B Cell Lymphomagenesis.

Cancer cell | 2018

The gene encoding the MEF2B transcription factor is mutated in germinal center (GC)-derived B cell lymphomas, but its role in GC development and lymphomagenesis is unknown. We demonstrate that Mef2b deletion reduces GC formation in mice and identify MEF2B transcriptional targets in GC, with roles in cell proliferation, apoptosis, GC confinement, and differentiation. The most common lymphoma-associated MEF2B mutant (MEF2BD83V) is hypomorphic, yet escapes binding and negative regulation by components of the HUCA complex and class IIa HDACs. Mef2bD83V expression in mice leads to GC enlargement and lymphoma development, a phenotype that becomes fully penetrant in combination with BCL2 de-regulation, an event associated with human MEF2B mutations. These results identify MEF2B as a critical GC regulator and a driver oncogene in lymphomagenesis.

Pubmed ID: 30205047 RIS Download

Antibodies used in this publication

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: P30 CA013696
  • Agency: NCI NIH HHS, United States
    Id: R01 CA172492
  • Agency: NCI NIH HHS, United States
    Id: R35 CA210105

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This is a list of tools and resources that we have found mentioned in this publication.


SAM format (tool)

RRID:SCR_012093

A generic alignment format for storing read alignments against reference sequences, supporting short and long reads (up to 128 Mbp) produced by different sequencing platforms.

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UCSC Genome Browser (tool)

RRID:SCR_012479

Portal to interactively visualize genomic data. Provides reference sequences and working draft assemblies for collection of genomes and access to ENCODE and Neanderthal projects. Includes collection of vertebrate and model organism assemblies and annotations, along with suite of tools for viewing, analyzing and downloading data.

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IMGT - the international ImMunoGeneTics information system (tool)

RRID:SCR_012780

A high-quality integrated knowledge resource specialized in the immunoglobulins (IG) or antibodies, T cell receptors (TR), major histocompatibility complex (MHC) of human and other vertebrate species, and in the immunoglobulin superfamily (IgSF), MHC superfamily (MhcSF) and related proteins of the immune system (RPI) of vertebrates and invertebrates, serving as the global reference in immunogenetics and immunoinformatics. IMGT provides a common access to sequence, genome and structure Immunogenetics data, based on the concepts of IMGT-ONTOLOGY and on the IMGT Scientific chart rules. IMGT works in close collaboration with EBI (Europe), DDBJ (Japan) and NCBI (USA). IMGT consists of sequence databases, genome database, structure database, and monoclonal antibodies database, Web resources and interactive tools.

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NIS-Elements (tool)

RRID:SCR_014329

Microscope imaging software suite used with Nikon products. NIS-Elements includes software applications for advanced and standard research, documentation, confocal microscopy, and high-content analysis.

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UCSC Genome Browser (tool)

RRID:SCR_005780

Portal to interactively visualize genomic data. Provides reference sequences and working draft assemblies for collection of genomes and access to ENCODE and Neanderthal projects. Includes collection of vertebrate and model organism assemblies and annotations, along with suite of tools for viewing, analyzing and downloading data.

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Anti-Histone H3 (tri methyl K4) antibody - ChIP Grade (antibody)

RRID:AB_306649

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Rabbit TrueBlot: Anti-Rabbit IgG HRP - 18-8816-33 (antibody)

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This monoclonal targets Rabbit TrueBlot: Anti-Rabbit IgG HRP

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Mouse TrueBlot ULTRA: Anti-Mouse Ig HRP - 18-8817-33 (antibody)

RRID:AB_2610851

This monoclonal targets Mouse TrueBlot ULTRA: Anti-Mouse Ig HRP

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Monoclonal Anti-Vinculin antibody produced in mouse (antibody)

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Pax-5 (C-20) (antibody)

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MEF-2B (M-84) (antibody)

RRID:AB_2142741

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IRF4-human (antibody)

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This polyclonal targets IRF4

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IgM (antibody)

RRID:AB_398464

This monoclonal targets IgM

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Anti-HIRA, clone WC119 (antibody)

RRID:AB_1977097

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HDAC9 antibody [EPR5223] (antibody)

RRID:AB_10861804

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HDAC7 (antibody)

RRID:AB_2716756

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H3K27ac-dmelanogaster (antibody)

RRID:AB_2614979

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CD3 (antibody)

RRID:AB_149924

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Bcl-2 (C 21) (antibody)

RRID:AB_2243455

This polyclonal targets BCL2

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Bcl-6 (antibody)

RRID:AB_10898007

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RRID:AB_2063450

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RRID:AB_476744

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SAMTOOLS (software resource)

RRID:SCR_002105

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RRID:SCR_007695

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HomoloGene (data or information resource)

RRID:SCR_002924

Automated system for constructing putative homology groups from complete gene sets of wide range of eukaryotic species. Databse that provides system for automatic detection of homologs, including paralogs and orthologs, among annotated genes of sequenced eukaryotic genomes. HomoloGene processing uses proteins from input organisms to compare and sequence homologs, mapping back to corresponding DNA sequences. Reports include homology and phenotype information drawn from Online Mendelian Inheritance in Man, Mouse Genome Informatics, Zebrafish Information Network, Saccharomyces Genome Database and FlyBase.

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Gene Set Enrichment Analysis (software resource)

RRID:SCR_003199

Software package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.

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HISAT2 (software resource)

RRID:SCR_015530

Graph-based alignment of next generation sequencing reads to a population of genomes.

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DAVID (software resource)

RRID:SCR_001881

Bioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.

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ChIPseeqer (software resource)

RRID:SCR_001545

Software that provides a comprehensive framework for the analysis of ChIP-seq data.

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Bowtie 2 (software resource)

RRID:SCR_016368

Ultrafast and memory efficient tool for aligning sequencing reads to long reference sequences. Supports gapped, local, and paired end alignment modes. More suited to finding longer, gapped alignments in comparison with original Bowtie method.

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ImageJ (software resource)

RRID:SCR_003070

Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.

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GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

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FlowJo (software resource)

RRID:SCR_008520

Software for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.

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DB (cell line)

RRID:CVCL_1168

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HEK293T (cell line)

RRID:CVCL_0063

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U-2932 (cell line)

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SU-DHL-4 (cell line)

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