Ikaros mediates gene silencing in T cells through Polycomb Repressive Complex 2 [ChIP-seq]

T cell development is accompanied by epigenetic changes that ensure the silencing of stem cell-related, and the activation of lymphocyte-specific programs. How transcription factors influence these changes remains unclear. We show that the Ikaros transcription factor interacts with the Polycomb Repressive Complex 2 (PRC2) in CD4-CD8- thymocytes, and allows its binding to >200 developmentally-regulated genes, many of which are expressed in hematopoietic stem cells. Loss of Ikaros in CD4-CD8- cells leads to diminished histone H3 Lys27 (H3K27) trimethylation and ectopic expression of these genes. Ikaros binding triggers PRC2 recruitment and H3K27 trimethylation. Furthermore, Ikaros interacts with PRC2 independently of the Nucleosome Remodeling and Deacetylation complex. Our results identify Ikaros as a fundamental regulator of PRC2 function in developing T cells.