Fiche publication
Date publication
janvier 2015
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CHAN Susan
,
Dr KASTNER Philippe
Tous les auteurs :
Oravecz A, Apostolov A, Polak K, Jost B, Le Gras S, Chan S, Kastner P
Lien Pubmed
Résumé
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.
Référence
Nat Commun. 2015 Nov 9;6:8823
