title: Ikaros mediates gene silencing in T cells through Polycomb repressive complex 2.
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.
authors.affiliation: 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.
authors.forename: Attila
authors.initials: A
authors.lastname: Oravecz
authors.affiliation: 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.
authors.forename: Apostol
authors.initials: A
authors.lastname: Apostolov
authors.affiliation: 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.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Polak
authors.affiliation: IGBMC Microarray and Sequencing Platform, Illkirch 67404, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Jost
authors.affiliation: IGBMC Microarray and Sequencing Platform, Illkirch 67404, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Le Gras
authors.affiliation: 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.
authors.forename: Susan
authors.initials: S
authors.lastname: Chan
authors.affiliation: 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.|Faculté de Médecine, Université de Strasbourg, Strasbourg 67000, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Kastner
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D047369:Chromatin Immunoprecipitation; D000066630:Ectopic Gene Expression; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D042421:Histone Code / Q000235:genetics; D006657:Histones / Q000378:metabolism; D051740:Ikaros Transcription Factor / Q000235:genetics* / Q000276:immunology; D008745:Methylation; D051379:Mice; D009707:Nucleosomes; D063151:Polycomb Repressive Complex 2 / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D060168:Thymocytes / Q000276:immunology*
chemical_list: D006657:Histones; D009707:Nucleosomes; C497238:Zfpn1a1 protein, mouse; D051740:Ikaros Transcription Factor; D063151:Polycomb Repressive Complex 2