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

Attila Oravecz (), Apostol Apostolov, Katarzyna Polak, Bernard Jost, Stéphanie Le Gras, Susan Chan () and Philippe Kastner ()
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Attila Oravecz: 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
Apostol Apostolov: 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
Katarzyna Polak: 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
Bernard Jost: IGBMC Microarray and Sequencing Platform
Stéphanie Le Gras: IGBMC Microarray and Sequencing Platform
Susan Chan: 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
Philippe Kastner: 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

Nature Communications, 2015, vol. 6, issue 1, 1-15

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms9823

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