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Harnessing of the nucleosome-remodeling-deacetylase complex controls lymphocyte development and prevents leukemogenesis
- Source :
- Nature immunology
- Publication Year :
- 2011
-
Abstract
- 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.
- Subjects :
- Cellular differentiation
Immunology
Article
Chromatin remodeling
03 medical and health sciences
Ikaros Transcription Factor
Mice
0302 clinical medicine
Immunology and Allergy
Nucleosome
Animals
Gene Regulatory Networks
Lymphocytes
Nucleotide Motifs
Transcription factor
030304 developmental biology
0303 health sciences
Leukemia
Thymocytes
biology
Base Sequence
Gene Expression Profiling
Cell Differentiation
Chromatin Assembly and Disassembly
Molecular biology
Mi-2/NuRD complex
Chromatin
Cell biology
Histone
030220 oncology & carcinogenesis
biology.protein
Mi-2 Nucleosome Remodeling and Deacetylase Complex
Protein Binding
Subjects
Details
- ISSN :
- 15292916
- Volume :
- 13
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature immunology
- Accession number :
- edsair.doi.dedup.....7514088c662e484ee92e089bd87e080b