@article{eb671db8d6844709b7988bbd92d863a6,
title = "Harnessing of the nucleosome-remodeling-deacetylase complex controls lymphocyte development and prevents leukemogenesis",
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.",
author = "Jiangwen Zhang and Jackson, {Audrey F.} and Taku Naito and Marei Dose and John Seavitt and Feifei Liu and Heller, {Elizabeth J.} and Mariko Kashiwagi and Toshimi Yoshida and Fotini Gounari and Petrie, {Howard T.} and Katia Georgopoulos",
note = "Funding Information: We thank P. Gomez for analysis of the expression of Mi-2β protein in thymocytes; the Kingston laboratory (Massachusetts General Hospital) for the hSWI-SNF complex and help with setting up the mononucleosome and 5S array assays; I. Joshi for help with cell sorting; B. Czyzewski for mouse husbandry; and B. Morgan for discussions of the project and critical review of the manuscript. Protein microsequencing was done at the Microchemistry and Proteomics Facility of Harvard University, Cambridge, and at the Taplin Mass Spectrometry Facility of Harvard Medical School, Boston, and high-throughput DNA sequencing and RNA profiling were done at the Bauer Center for Genomic Research of Harvard University, Cambridge. Supported by the US National Institutes of Health (2T32AI007529 to A.F.J.; and 5R01AI042254 and R01CA158006 to K.G.).",
year = "2012",
month = jan,
doi = "10.1038/ni.2150",
language = "English (US)",
volume = "13",
pages = "86--94",
journal = "Nature immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "1",
}