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GSE61881
Mus musculus, Homo sapiens
19 Downloadable Samples
Affymetrix HT MG-430 PM Array Plate (htmg430pm), Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Macrophages are amongst the major targets of glucocorticoids (GC) as therapeutic anti-inflammatory agents. Here we show that GC treatment of mouse and human macrophages initiates a cascade of induced gene expression including many anti-inflammatory genes. Inducible binding of the glucocorticoid receptor (GR) was detected at candidate enhancers in the vicinity of induced genes in both species and this was strongly associated with canonical GR binding motifs. However, the sets of inducible genes, the candidate enhancers, and the GR motifs within them, were highly-divergent between the two species.
Publication Title
Enhancer Turnover Is Associated with a Divergent Transcriptional Response to Glucocorticoid in Mouse and Human Macrophages.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Time
View Samples- Homo sapiens
- 19 Downloadable Samples
Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm), Affymetrix HT MG-430 PM Array Plate (htmg430pm)
Description
Macrophages are amongst the major targets of glucocorticoids (GC) as therapeutic anti-inflammatory agents. Here we show that GC treatment of mouse and human macrophages initiates a cascade of induced gene expression including many anti-inflammatory genes. Inducible binding of the glucocorticoid receptor (GR) was detected at candidate enhancers in the vicinity of induced genes in both species and this was strongly associated with canonical GR binding motifs. However, the sets of inducible genes, the candidate enhancers, and the GR motifs within them, were highly-divergent between the two species.. The data cast further doubt upon the predictive value of mouse models of inflammatory disease.
Publication Title
Enhancer Turnover Is Associated with a Divergent Transcriptional Response to Glucocorticoid in Mouse and Human Macrophages.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To study the effect of balanced chromosomal rearrangements on gene expression, we compared the transcriptomes of cell lines from control and t(11;22)(q23;q11) individuals. This translocation between chromosomes 11 and 22 is the only recurrent constitutional non-Robertsonian translocation in humans. The number of differentially expressed transcripts between the translocated and control cohort is significantly higher than that observed between control samples alone, suggesting that balanced rearrangements have a greater effect on gene expression than normal variation. Altered expression is not limited to genes close to the translocation breakpoint suggesting that a long-range effect is operating. Indeed we show that the nuclear position of the derivative chromosome is altered compared to the normal chromosomes. Our results are consistent with recent studies that indicate a functional role for nuclear position in regulating the expression of some genes in mammalian cells. They may also have implications on reproductive separation, as we show that reciprocal translocations not only provide partial isolation for speciation but also significant changes in transcriptional regulation through alteration of nuclear chromosomes territories.
Publication Title
The effect of translocation-induced nuclear reorganization on gene expression.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 31 Downloadable Samples
NextSeq 550
Description
Nascent RNA was metabolically labelled with 4SU in undifferentiated and ESC-derived neural progenitor cells (NPCs). 4SU incorporated RNA was isolated and deep-sequenced at day 0 (ESCs), 3, 5 and 7 of differentiation. NPC differentiation was monitored through expression of a GFP reporter insereted into the Sox1 locus (46C reporter ESC line; PMID: 12524553). The aim was to monitor changes in transcription as ESCs differentiate into NPCs and relate this to enhancer activity. Overall design: For each of the 4 differentiation time points, two independent biological replicates were prepared and sequenced. For each assayed time point, both merged and individual replicate 4SU-seq profiles were generated.
Publication Title
Decreased Enhancer-Promoter Proximity Accompanying Enhancer Activation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Whereas DNA methylation is essential for genomic imprinting, the importance of histone methylation in the allelic repression of imprinted genes is unclear. Imprinting control regions (ICRs), however, are consistently marked by histone H3 K9 methylation on their DNA-methylated allele. In the placenta, the paternal silencing along the Kcnq1 domain on distal chromosome 7 also correlates with the presence of H3-K9 methylation, but imprinted repression at these genes is maintained independently of DNA methylation. To explore which histone methyltransferase (HMT) could mediate the allelic H3-K9 methylation on distal chromosome 7, and at ICRs, we generated mouse conceptuses deficient for the SET-domain protein G9a. We find that in the embryo and placenta, the differential DNA methylation at ICRs and imprinted genes is maintained in the absence of G9a. Accordingly, in embryos, imprinted gene expression is unchanged at the domains analysed, in spite of a global loss of H3-K9 di-methylation (H3K9me2). In contrast, the placenta-specific imprinting of genes on distal chromosome 7 is lost in the absence of G9, and this correlates with a loss of H3K9me2 and H3K9me3. These findings provide the first in vivo evidence for the involvement of a SET domain protein in imprinting and highlight the importance of histone lysine methylation rather than DNA methylation in the maintenance of imprinting in the trophoblast lineage.
Publication Title
G9a histone methyltransferase contributes to imprinting in the mouse placenta.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- NextSeq 550
Description
WT J1 and 3B3L cells (in which Dnmt3B and Dnm3L are constitutively expressed from an exogenous construct) were cultured under both serum/LIF and 2i/LIF conditions. 3B3L cells do not show ground state-associated hypomethylation phenotype. This experiment sought to analyse the gene expression changes between the two conditions. Overall design: Three biological replicates per condition J1 serum, J1 2i, 3B3-3l serum, 3B3-3l 2i.
Publication Title
DNA Methylation Directs Polycomb-Dependent 3D Genome Re-organization in Naive Pluripotency.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Two distinct Polycomb complexes, PRC1 and PRC2, collaborate to maintain epigenetic repression of key developmental loci in embryonic stem cells (ESCs). PRC1 and PRC2 have histone modifying activities, catalyzing mono-ubiquitination of histone H2A (H2AK119u1) and trimethylation of H3 lysine 27 (H3K27me3) respectively. Compared to H3K27me3, localization and role of H2AK119ub1 is not fully understood in ESCs. Here we present genome-wide H2AK119u1 maps in ESCs and identify a group of genes at which H2AK119u1 is deposited in a Ring1-dependent manner. These genes are a distinctive subset of genes with H3K27me3 enrichment and are the central targets of Polycomb silencing that are required to maintain ESC identity. We further show that the H2A ubiquitination activity of PRC1 is dispensable for its target binding and its activity to compact chromatin at Hox loci, but is indispensable for efficient repression of target genes and thereby ESC maintenance. These data demonstrate that multiple effector mechanisms including H2A ubiquitination and chromatin compaction combine to mediate PRC1-dependent repression of genes that are crucial for the maintenance of ESC identity. Utilization of these diverse effector mechanisms might provide a means to maintain a repressive state that is robust yet highly responsive to developmental cues during ES cell self-renewal and differentiation.
Publication Title
Histone H2A mono-ubiquitination is a crucial step to mediate PRC1-dependent repression of developmental genes to maintain ES cell identity.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We used microarrays to investigate the restoration of repression of PRC1 target gene expression in Ring1A/B-dKO ES cells stably expressing either of mock, WT or mutant Ring1B construct.
Publication Title
Histone H2A mono-ubiquitination is a crucial step to mediate PRC1-dependent repression of developmental genes to maintain ES cell identity.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Redistribution of H3K27me3 upon DNA hypomethylation results in de-repression of Polycomb target genes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
DNA methylation and the Polycomb Repression System are epigenetic mechanisms that play important roles in maintaining transcriptional repression. Recent evidence suggests that DNA methylation can attenuate the binding of Polycomb protein components to chromatin and thus plays a role in determining their genomic targeting. However, whether this role of DNA methylation is important in the context of transcriptional regulation is unclear. By genome-wide mapping of the Polycomb Repressive Complex 2 (PRC2)-signature histone mark, H3K27me3, in severely DNA hypomethylated mouse somatic cells, we show that hypomethylation leads to widespread H3K27me3 redistribution, in a manner that reflects the local DNA methylation status in wild-type cells. Unexpectedly, we observe striking loss of H3K27me3 and PRC2 from Polycomb-target gene promoters in DNA hypomethylated cells, including Hox gene clusters. Importantly, we show that many of these genes become ectopically expressed in DNA hypomethylated cells, consistent with loss of Polycomb-mediated repression. An intact DNA methylome is required for appropriate Polycomb-mediated gene repression by constraining PRC2 targeting. These observations identify a previously unappreciated role for DNA methylation in gene regulation and therefore influence our understanding of how this epigenetic mechanism contributes to normal development and disease.
Publication Title
Redistribution of H3K27me3 upon DNA hypomethylation results in de-repression of Polycomb target genes.
Sample Metadata Fields
Specimen part
View Samples