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
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Source species Mus musculus
Contributed by Jernej Godec (Dana-Farber Cancer Institute)
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Version history 7.3: Moved to ImmuneSigDB sub-collection.

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