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GSE46545
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st), Illumina HiSeq 2000
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The histone H3 lysine 9 methyltransferases G9a and GLP regulate polycomb repressive complex 2-mediated gene silencing.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
G9a/GLP and Polycomb Repressive Complex 2 (PRC2) are two major epigenetic silencing machineries, which in particular methylate histone H3 on lysines 9 and 27 (H3K9 and H3K27), respectively. Although evidence of a crosstalk between H3K9 and H3K27 methylations has started to emerge, their actual interplay remains elusive. Here, we show that PRC2 and G9a/GLP interact physically and functionally. Moreover, combining different genome-wide approaches, we demonstrate that Ezh2 and G9a/GLP share an important number of common genomic targets, encoding developmental and neuronal regulators. Furthermore, we show that G9a enzymatic activity modulates PRC2 genomic recruitment to a subset of its target genes. Taken together, our findings demonstrate an unanticipated interplay between two main histone lysine methylation mechanisms, which cooperate to maintain silencing of a subset of developmental genes.
Publication Title
The histone H3 lysine 9 methyltransferases G9a and GLP regulate polycomb repressive complex 2-mediated gene silencing.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
G9a/GLP and Polycomb Repressive Complex 2 (PRC2) are two major epigenetic silencing machineries, which in particular methylate histone H3 on lysines 9 and 27 (H3K9 and H3K27), respectively. Although evidence of a crosstalk between H3K9 and H3K27 methylations has started to emerge, their actual interplay remains elusive. Here, we show that PRC2 and G9a/GLP interact physically and functionally. Moreover, combining different genome-wide approaches, we demonstrate that Ezh2 and G9a/GLP share an important number of common genomic targets, encoding developmental and neuronal regulators. Furthermore, we show that G9a enzymatic activity modulates PRC2 genomic recruitment to a subset of its target genes. Taken together, our findings demonstrate an unanticipated interplay between two main histone lysine methylation mechanisms, which cooperate to maintain silencing of a subset of developmental genes. Overall design: RNA-seq has been perform in triplicate on mES cell (TT2 : Wildtype, and KO G9a-/-)
Publication Title
The histone H3 lysine 9 methyltransferases G9a and GLP regulate polycomb repressive complex 2-mediated gene silencing.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Schizosaccharomyces pombe
- 2 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
To estimate mRNA steady-state levels we used RNA extracted from logarithmically growing fisson yeast cells on Affymetrix Yeast 2.0 Genechip arrays. The signal intensities from two independent biological repeats were averaged, resulting in measurements for 4818 out of 4962 nuclear protein-coding genes.
Publication Title
A network of multiple regulatory layers shapes gene expression in fission yeast.
Sample Metadata Fields
Sex, Subject
View Samples- Homo sapiens
- 41 Downloadable Samples
- Illumina HiSeq 2500
Description
using RNA-seq we characterized gene expression changes occuring upon knockout of BAP1, ASXL1, ASXL2, ASXL1/2 or Polycomb genes RING1B and EZH2. We also investigated the response to retinoic acid treatment in wild-type and BAP1 KO cells. Overall design: Examination of transcript abundance in wild-type HAP1 cells and in 9 different HAP1-mutated cell lines as well as upon retinoic acid treatment in wild-type and BAP1 KO cells. Two biological replicated were performed for each condition.
Publication Title
BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Characterization of gene expression changes occuring upon knockout of RING1A, RING1B, and BAP1. Overall design: Four Samples
Publication Title
BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
We report application of RNA-seq to quantify gene expression changes in fasted mouse livers compared to re-fed controls. Overall design: RNA-seq from livers of re-fed and 48h fasted mice.
Publication Title
Histone propionylation is a mark of active chromatin.
Sample Metadata Fields
Sex, Specimen part, Treatment, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Alterations of chromatin modifiers are frequent in cancer but their functional consequences remain often unclear. Focusing on the Polycomb protein EZH2 that deposits H3K27me3 mark, we showed that its high expression in solid tumors is a consequence, and not a cause, of tumorigenesis. In mouse and human models, EZH2 is dispensable for prostate cancer development and restrains breast tumorigenesis. High EZH2 expression in tumors results from a tight coupling to proliferation to ensure H3K27me3 homeostasis. However, this process is malfunctioning in breast cancer. Low EZH2 expression relative to proliferation and mutations in Polycomb genes are actually of poor prognosis and occur in metastases. We show that while altered EZH2 activity consistently modulates a subset of its target genes, it promotes a wider transcriptional instability. Importantly, transcriptional changes consequent to EZH2 loss are predominantly irreversible. Our study provides an unexpected understanding of EZH2's contribution to solid tumors with important therapeutic implications.
Publication Title
Impaired PRC2 activity promotes transcriptional instability and favors breast tumorigenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Polycomb Repressive Complex 2 (PRC2) plays a key role in controlling transcriptional repression. It is thought to act at the level of the chromatin, where its enzymatic subunits Ezh1 and Ezh2 catalyse the di/tri-methylation of histone H3 on its lysine 27 (H3K27me3).
Publication Title
Impaired PRC2 activity promotes transcriptional instability and favors breast tumorigenesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 16 Downloadable Samples
- Illumina HiSeq 2500
Description
Using RNA-seq we characterized gene expression changes occuring upon knockout of EZH2, EZH1, EZH1+EZH2 or SUZ12 in a neurofibroma cell line. We also investigated the transcriptional consequences of EZH1+EZH2 double knockout in a SUZ12-mutant MPNST cell line. Overall design: Examination of transcript abundance in wild-type and mutant ipNF05.5 or 88.14 cells. Two biological replicates were performed for wild-type and mutant ipNF05.5 cell lines. Three biological replicates were performed for wild-type and mutant 88.14 cell lines.
Publication Title
EZH1/2 function mostly within canonical PRC2 and exhibit proliferation-dependent redundancy that shapes mutational signatures in cancer.
Sample Metadata Fields
Cell line, Subject
View Samples