期刊
NATURE IMMUNOLOGY
卷 13, 期 1, 页码 86-U132出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.2150
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- US National Institutes of Health [2T32AI007529, 5R01AI042254, R01CA158006]
- NATIONAL CANCER INSTITUTE [R01CA162092, R01CA158006] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI042254, R37AI033062, T32AI007529] Funding Source: NIH RePORTER
Cell fate depends on the interplay between chromatin regulators and transcription factors. Here we show that activity of the Mi-2 beta 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.
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