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Harnessing of the nucleosome-remodeling-deacetylase complex controls lymphocyte development and prevents leukemogenesis.

Nature immunology | 2011

Cell fate depends on the interplay between chromatin regulators and transcription factors. Here we show that activity of the Mi-2β nucleosome-remodeling and histone-deacetylase (NuRD) complex was controlled by the Ikaros family of lymphoid lineage-determining proteins. Ikaros, an integral component of the NuRD complex in lymphocytes, tethered this complex to active genes encoding molecules involved in lymphoid differentiation. Loss of Ikaros DNA-binding activity caused a local increase in chromatin remodeling and histone deacetylation and suppression of lymphoid cell-specific gene expression. Without Ikaros, the NuRD complex also redistributed to transcriptionally poised genes that were not targets of Ikaros (encoding molecules involved in proliferation and metabolism), which induced their reactivation. Thus, release of NuRD from Ikaros regulation blocks lymphocyte maturation and mediates progression to a leukemic state by engaging functionally opposing epigenetic and genetic networks.

Pubmed ID: 22080921 RIS Download

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Associated grants

  • Agency: NCI NIH HHS, United States
    Id: R01 CA158006
  • Agency: NCI NIH HHS, United States
    Id: R01 CA162092
  • Agency: NCI NIH HHS, United States
    Id: R01 CA162092-20
  • Agency: NIAID NIH HHS, United States
    Id: R37 AI033062-18
  • Agency: NIAID NIH HHS, United States
    Id: R37 AI033062
  • Agency: NIAID NIH HHS, United States
    Id: 5R01AI042254
  • Agency: NIAID NIH HHS, United States
    Id: 2T32AI007529
  • Agency: NCI NIH HHS, United States
    Id: R01CA158006
  • Agency: NIAID NIH HHS, United States
    Id: T32 AI007529
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI042254

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ChIP-seq (tool)

RRID:SCR_001237

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RRID:SCR_010881

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RRID:SCR_010943

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