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Ikaros mediates gene silencing in T cells through Polycomb Repressive Complex 2

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE61149 | GEO | 2015/11/03

SECONDARY ACCESSION(S): PRJNA260351

REPOSITORIES: GEO

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Ikaros mediates gene silencing in T cells through Polycomb Repressive Complex 2

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-11-03 | E-GEOD-61149 | biostudies-arrayexpress

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

Project description: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.

| S-EPMC4667618 | biostudies-literature

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

Project description: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. Genome-wide comparison of different histone modifications, Ikaros, Suz12 and NuRD binding in different stages of T cell development in WT and Ikaros mutant mice. Profiling of H3K27me3 in DN1, DN2, DN3, DN4 and DP thymocytes and hematopoietic stem and progenitor cells (LSK cells) of WT and Ikaros mutant mice. Profiling of H3K4me3 and H3ac in WT and Ikaros mutant DP thymocytes. Global analysis of Ikaros binding in WT DN3, DN4 and DP cells, Suz12 binding in WT and Ikaros mutant DN3 cells, and Mta2 and Mi2beta binding in WT DN3 cells. Genome-wide profiling of Ikaros binding and H3K27me3 upon Ikaros activation in Ikaros-deficient leukemic T cells.

2015-11-03 | E-GEOD-61148 | biostudies-arrayexpress

Gene silencing triggers Polycomb Repressive Complex 2 recruitment to CpG islands genome-wide

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-07-03 | E-GEOD-58023 | biostudies-arrayexpress

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

2015-11-03 | GSE61148 | GEO

A repressive H3K36me2 reader mediates Polycomb silencing.

Project description:In animals, evolutionarily conserved Polycomb repressive complex 2 (PRC2) catalyzes histone H3 lysine 27 trimethylation (H3K27me3) and PRC1 functions in recruitment and transcriptional repression. However, the mechanisms underlying H3K27me3-mediated stable transcriptional silencing are largely unknown, as PRC1 subunits are poorly characterized in fungi. Here, we report that in the filamentous fungus Magnaporthe oryzae, the N-terminal chromodomain and C-terminal MRG domain of Eaf3 play key roles in facultative heterochromatin formation and transcriptional silencing. Eaf3 physically interacts with Ash1, Eed, and Sin3, encoding an H3K36 methyltransferase, the core subunit of PRC2, and a histone deacetylation co-suppressor, respectively. Eaf3 co-localizes with a set of repressive Ash1-H3K36me2 and H3K27me3 loci and mediates their transcriptional silencing. Furthermore, Eaf3 acts as a histone reader for the repressive H3K36me2 and H3K27me3 marks. Eaf3-occupied regions are associated with increased nucleosome occupancy, contributing to transcriptional silencing in M. oryzae. Together, these findings reveal that Eaf3 is a repressive H3K36me2 reader and plays a vital role in Polycomb gene silencing and the formation of facultative heterochromatin in fungi.

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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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LATS2 regulates repressive epigenetic integrity via regulation of Polycomb repressive complex 2

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The Histone H3 Lysine 9 Methyltransferases G9a and GLP Regulate Polycomb Repressive Complex 2-Mediated Gene Silencing

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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Role of polycomb repressive complex 1 in the intestinal homeostasis

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series