Human Gene Set: GSE10273_HIGH_IL7_VS_HIGH_IL7_AND_IRF4_IN_IRF4_8_NULL_PRE_BCELL_DN


Standard name GSE10273_HIGH_IL7_VS_HIGH_IL7_AND_IRF4_IN_IRF4_8_NULL_PRE_BCELL_DN
Systematic name M317
Brief description Genes down-regulated in IRF4 and IRF8 [GeneID=3662;3394] null pre-B cell treated with 5ng/ml IL7 [GeneID=3574] versus those transduced with IRF4 [GeneID=3662].
Full description or abstract Productive rearrangement of the immunoglobulin heavy chain locus triggers a major developmental checkpoint that promotes limited clonal expansion of pre-B cells, culminating in cell cycle arrest and rearrangement of the kappa (?) or lambda (?) light-chain loci. B lineage cells lacking the related transcription factors IRF-4 and IRF-8 undergo a developmental arrest at the cycling pre-B cell stage and are blocked for light-chain recombination. Using Irf-4,8-/- pre-B cells we demonstrate that two pathways converge to synergistically drive light-chain rearrangement, a process that is not simply activated by cell cycle exit. One pathway is directly dependent on IRF-4, whose expression is elevated by pre-BCR signaling. IRF-4 targets the ? 3? and ? enhancers to increase locus accessibility and positions a kappa allele away from pericentromeric heterochromatin. The other pathway is triggered by attenuation of IL-7 signaling and results in activation of the ? intronic enhancer via binding of the transcription factor, E2A. Intriguingly, IRF-4 regulates the expression of CXCR4 and promotes the migration of pre-B cells in response to the chemokine CXCL12. We propose that IRF-4 coordinates the two pathways regulating light-chain recombination by positioning pre-B cells away from IL-7 expressing stromal cells. We used microarrys to identify the changes in gene expression under different levels of the cytokine IL-7 and after rescue of genetic defect.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 18280186   Authors: Johnson K,Hashimshony T,Sawai CM,Pongubala JM,Skok JA,Aifantis I,Singh H
Exact source GSE10273_2544_200_DN
Related gene sets (show 5 additional gene sets from the source publication)

(show 48 gene sets from any of these authors)
External links
Filtered by similarity ?
Source species Mus musculus
Contributed by Jernej Godec (Dana-Farber Cancer Institute)
Source platform or
identifier namespace		 HUMAN_GENE_SYMBOL
Dataset references (show 1 datasets)
Download gene set format: grp | gmt | xml | json | TSV metadata
Compute overlaps ? (show collections to investigate for overlap with this gene set)
Compendia expression profiles ? NG-CHM interactive heatmaps
(Please note that clustering takes a few seconds)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)

Legacy heatmaps (PNG)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 200 genes
Gene families ? Categorize these 200 genes by gene family
Show members (show 200 source identifiers mapped to 200 genes)
Version history 7.3: Moved to ImmuneSigDB sub-collection.


Creative Commons Attribution 4.0 International License (CC-BY-4.0)

The contents of this gene set are protected by copyright (c) 2004-2026 Broad Institute, Inc., Massachusetts Institute of Technology, and Regents of the University of California, subject to the terms and conditions of the Creative Commons Attribution 4.0 International License.

See the full MSigDB license terms here.