Spatial interplay between Polycomb and Trithorax complexes controls transcriptional activity in T lymphocytes
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE73825 | GEO | 2015/10/10
SECONDARY ACCESSION(S): PRJNA298056
REPOSITORIES: GEO
Similar Datasets
Project description:Trithorax group (TrxG) and Polycomb group (PcG) proteins are two mutually antagonistic chromatin modifying complexes, however, how they together mediate transcriptional counter-regulation remains unknown. Genome-wide analysis revealed that binding of Ezh2 and menin, central members of the PcG and TrxG complexes, respectively, were reciprocally correlated. Moreover, we identified a developmental change in the positioning of Ezh2 and menin in differentiated T lymphocytes compared to embryonic stem cells. Ezh2-binding upstream and menin-binding downstream of the transcription start site was frequently found at genes with higher transcriptional levels, and Ezh2-binding downstream and menin-binding upstream was found at genes with lower expression in T lymphocytes. Interestingly, of the Ezh2 and menin cooccupied genes, those exhibiting occupancy at the same position displayed greatly enhanced sensitivity to loss of Ezh2. Finally, we also found that different combinations of Ezh2 and menin occupancy were associated with expression of specific functional gene groups important for T cell development. Therefore, spatial cooperative gene regulation by the PcG and TrxG complexes may represent a novel mechanism regulating the transcriptional identity of differentiated cells.
| S-EPMC4609743 | biostudies-literature
Project description:Trithorax group (TrxG) and Polycomb group (PcG) proteins are two mutually antagonistic chromatin modifying complexes, however, how they together mediate transcriptional counterregulation remains unknown. Genome-wide analysis revealed that binding of Ezh2 and Menin, central members of the PcG and TrxG complexes, respectively, were reciprocally correlated. Moreover, we identified a developmental change in the positioning of Ezh2 and Menin in differentiated T lymphocytes compared to embryonic stem cells. Ezh2-binding upstream and Menin-binding downstream of the transcription start site (TSS) was frequently found at genes with higher transcriptional levels, and Ezh2-binding downstream and Menin-binding upstream was found at genes with lower expression in T lymphocytes. Interestingly, of the Ezh2 and Menin co-occupied genes, those exhibiting occupancy at the same position displayed greatly enhanced sensitivity to loss of Ezh2. Finally, we also found that different combinations of Ezh2 and Menin occupancy were associated with expression of specific functional gene groups important for T cell development. Therefore, spatial cooperative gene regulation by the PcG and TrxG complexes may represent a novel mechanism regulating the transcriptional identity of differentiated cells. ES cells, B cells and T cells are profiled for mRNA expression
2015-09-08 | E-GEOD-72757 | biostudies-arrayexpress
Project description:Trithorax group (TrxG) and Polycomb group (PcG) proteins are two mutually antagonistic chromatin modifying complexes, however, how they together mediate transcriptional counterregulation remains unknown. Genome-wide analysis revealed that binding of Ezh2 and Menin, central members of the PcG and TrxG complexes, respectively, were reciprocally correlated. Moreover, we identified a developmental change in the positioning of Ezh2 and Menin in differentiated T lymphocytes compared to embryonic stem cells. Ezh2-binding upstream and Menin-binding downstream of the transcription start site (TSS) was frequently found at genes with higher transcriptional levels, and Ezh2-binding downstream and Menin-binding upstream was found at genes with lower expression in T lymphocytes. Interestingly, of the Ezh2 and Menin co-occupied genes, those exhibiting occupancy at the same position displayed greatly enhanced sensitivity to loss of Ezh2. Finally, we also found that different combinations of Ezh2 and Menin occupancy were associated with expression of specific functional gene groups important for T cell development. Therefore, spatial cooperative gene regulation by the PcG and TrxG complexes may represent a novel mechanism regulating the transcriptional identity of differentiated cells.
2015-10-10 | GSE72757 | GEO
Project description:Trithorax group (TrxG) and Polycomb group (PcG) proteins are two mutually antagonistic chromatin modifying complexes, however, how they together mediate transcriptional counterregulation remains unknown. Genome-wide analysis revealed that binding of Ezh2 and Menin, central members of the PcG and TrxG complexes, respectively, were reciprocally correlated. Moreover, we identified a developmental change in the positioning of Ezh2 and Menin in differentiated T lymphocytes compared to embryonic stem cells. Ezh2-binding upstream and Menin-binding downstream of the transcription start site (TSS) was frequently found at genes with higher transcriptional levels, and Ezh2-binding downstream and Menin-binding upstream was found at genes with lower expression in T lymphocytes. Interestingly, of the Ezh2 and Menin co-occupied genes, those exhibiting occupancy at the same position displayed greatly enhanced sensitivity to loss of Ezh2. Finally, we also found that different combinations of Ezh2 and Menin occupancy were associated with expression of specific functional gene groups important for T cell development. Therefore, spatial cooperative gene regulation by the PcG and TrxG complexes may represent a novel mechanism regulating the transcriptional identity of differentiated cells.
2015-10-10 | GSE73820 | GEO
Project description:Trithorax group (TrxG) and Polycomb group (PcG) proteins are two mutually antagonistic chromatin modifying complexes, however, how they together mediate transcriptional counterregulation remains unknown. Genome-wide analysis revealed that binding of Ezh2 and Menin, central members of the PcG and TrxG complexes, respectively, were reciprocally correlated. Moreover, we identified a developmental change in the positioning of Ezh2 and Menin in differentiated T lymphocytes compared to embryonic stem cells. Ezh2-binding upstream and Menin-binding downstream of the transcription start site (TSS) was frequently found at genes with higher transcriptional levels, and Ezh2-binding downstream and Menin-binding upstream was found at genes with lower expression in T lymphocytes. Interestingly, of the Ezh2 and Menin co-occupied genes, those exhibiting occupancy at the same position displayed greatly enhanced sensitivity to loss of Ezh2. Finally, we also found that different combinations of Ezh2 and Menin occupancy were associated with expression of specific functional gene groups important for T cell development. Therefore, spatial cooperative gene regulation by the PcG and TrxG complexes may represent a novel mechanism regulating the transcriptional identity of differentiated cells.
2015-10-10 | GSE73813 | GEO
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Project description:Polycomb group (PcG) and trithorax group (trxG) proteins are key regulators of homeotic genes and have crucial roles in cell proliferation, growth and development. PcG and trxG proteins form higher order protein complexes that contain SET domain proteins, with a histone methyltransferase (HMTase) activity, responsible for the different types of lysine methylation at the N-terminal tails of the core histone proteins. In recent years, genetic studies along with biochemical and cell biological analyses in Arabidopsis have enabled researchers to begin to understand how PcG and trxG proteins are recruited to chromatin and how they regulate their target genes and to elucidate their functions. This review focuses on the advances in our understanding of the biological roles of PcG and trxG proteins, their molecular mechanisms of action and further examines the role of histone marks in PcG and trxG regulation in Arabidopsis.
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Project description:Polycomb group (PcG) and Trithorax group (TrxG) genes encode important regulators of development and differentiation in metazoans. These two groups of genes were discovered in Drosophila by their opposing effects on homeotic gene (Hox) expression. PcG genes collectively behave as genetic repressors of Hox genes, while the TrxG genes are necessary for HOX gene expression or function. Biochemical studies showed that many PcG proteins are present in two protein complexes, Polycomb repressive complexes 1 and 2, which repress transcription via chromatin modifications. TrxG proteins activate transcription via a variety of mechanisms. Here we summarize the large body of genetic and biochemical experiments in Drosophila on these two important groups of genes.
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Project description:cis-Regulatory DNA elements contain multiple binding sites for activators and repressors of transcription. Among these elements are enhancers, which establish gene expression states, and Polycomb/Trithorax response elements (PREs), which take over from enhancers and maintain transcription states of several hundred developmentally important genes. PREs are essential to the correct identities of both stem cells and differentiated cells. Evolutionary differences in cis-regulatory elements are a rich source of phenotypic diversity, and functional binding sites within regulatory elements turn over rapidly in evolution. However, more radical evolutionary changes that go beyond motif turnover have been difficult to assess. We used a combination of genome-wide bioinformatic prediction and experimental validation at specific loci, to evaluate PRE evolution across four Drosophila species. Our results show that PRE evolution is extraordinarily dynamic. First, we show that the numbers of PREs differ dramatically between species. Second, we demonstrate that functional binding sites within PREs at conserved positions turn over rapidly in evolution, as has been observed for enhancer elements. Finally, although it is theoretically possible that new elements can arise out of nonfunctional sequence, evidence that they do so is lacking. We show here that functional PREs are found at nonorthologous sites in conserved gene loci. By demonstrating that PRE evolution is not limited to the adaptation of preexisting elements, these findings document a novel dimension of cis-regulatory evolution.
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