Format

Send to

Choose Destination
Nat Immunol. 2011 Nov 13;13(1):86-94. doi: 10.1038/ni.2150.

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

Author information

1
FAS Research Computing, Harvard University, Cambridge, MA 02138, USA.
2
CBRC, Mass General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
3
Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
4
Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458, USA.
#
Contributed equally

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.

Comment in

PMID:
22080921
PMCID:
PMC3868219
DOI:
10.1038/ni.2150
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center