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Nat Commun. 2015 Nov 9;6:8823. doi: 10.1038/ncomms9823.

Ikaros mediates gene silencing in T cells through Polycomb repressive complex 2.

Author information

1
Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR 7104, Université de Strasbourg, Equipe Labellisée Ligue Contre le Cancer, 1 rue Laurent Fries, Illkirch 67404, France.
2
IGBMC Microarray and Sequencing Platform, Illkirch 67404, France.
3
Faculté de Médecine, Université de Strasbourg, Strasbourg 67000, France.

Abstract

T-cell development is accompanied by epigenetic changes that ensure the silencing of stem cell-related genes and the activation of lymphocyte-specific programmes. How transcription factors influence these changes remains unclear. We show that the Ikaros transcription factor forms a complex with Polycomb repressive complex 2 (PRC2) in CD4(-)CD8(-) thymocytes and allows its binding to more than 500 developmentally regulated loci, including those normally activated in haematopoietic stem cells and others induced by the Notch pathway. Loss of Ikaros in CD4(-)CD8(-) cells leads to reduced histone H3 lysine 27 trimethylation and ectopic gene expression. Furthermore, Ikaros binding triggers PRC2 recruitment and Ikaros interacts with PRC2 independently of the nucleosome remodelling and deacetylation complex. Our results identify Ikaros as a fundamental regulator of PRC2 function in developing T cells.

PMID:
26549758
PMCID:
PMC4667618
DOI:
10.1038/ncomms9823
[Indexed for MEDLINE]
Free PMC Article

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