Harnessing of the nucleosome-remodeling-deacetylase complex controls lymphocyte development and prevents leukemogenesis
Autor: | Taku Naito, Audrey F. Jackson, Marei Dose, John Seavitt, Jiangwen Zhang, Feifei Liu, Fotini Gounari, Howard T. Petrie, Elizabeth J. Heller, Toshimi Yoshida, Katia Georgopoulos, Mariko Kashiwagi |
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Rok vydání: | 2011 |
Předmět: |
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 |
Zdroj: | Nature immunology |
ISSN: | 1529-2916 |
Popis: | 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. |
Databáze: | OpenAIRE |
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