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GSE12889
Homo sapiens
2 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Insulators are DNA elements, which prevent inappropriate interactions between the neighboring regions of the genome. They can be functionally classified as either enhancer blockers or domain barriers. CTCF (CCCTC binding factor) is the only known major insulator binding protein in the vertebrates and has been shown to bind many enhancer-blocking elements. However, it is not clear whether it plays a role in chromatin domain barriers between active and repressive domains. Here, we used ChIP-Seq to map the genome-wide binding sites of CTCF in three cell types and identified significant binding of CTCF to the boundaries of repressive chromatin domains marked by H3K27me3. Although we find an extensive overlapping of CTCF binding sites across the three cell types, its association with the domain boundaries is cell type-specific. We further show that the nucleosomes flanking CTCF binding sites are well positioned and associated with histone H2AK5 acetylation (H2AK5ac). Interestingly, we found a complementary pattern between the repressive H3K27me3 and the active H2AK5ac regions, which are separated by CTCF. Our findings indicate that CTCF may play important roles in the barrier activity of insulators and provide a resource for further investigation of the CTCF function in organizing chromatin in the human genome.
Publication Title
Global analysis of the insulator binding protein CTCF in chromatin barrier regions reveals demarcation of active and repressive domains.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina Genome Analyzer II
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Acute depletion of Tet1-dependent 5-hydroxymethylcytosine levels impairs LIF/Stat3 signaling and results in loss of embryonic stem cell identity.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina Genome Analyzer II
Description
The TET family of FE(II) and 2-oxoglutarate-dependent enzymes (Tet1/2/3) promote DNA demethylation by converting 5-methylcytosine to 5-hydroxymethylcytosine (5hmC), which they further oxidize into 5-formylcytosine and 5-carboxylcytosine. Tet1 is robustly expressed in mouse embryonic stem cells (mESCs) and has been implicated in mESC maintenance. Here we demonstrate that, unlike genetic deletion, RNAi-mediated depletion of Tet1 in mESCs led to a significant reduction in 5hmC and loss of mESC identity. The differentiation phenotype due to Tet1 depletion positively correlated with the extent of 5hmC loss. Meta-analyses of genomic datasets suggested interaction between Tet1 and leukemia inhibitory factor (LIF) signaling. LIF signaling is known to promote self-renewal and pluripo-tency in mESCs partly by opposing MAPK/ERK mediated differentiation. Withdrawal of LIF leads to differentiation of mESCs. We discovered that Tet1 depletion impaired LIF-dependent Stat3-mediated gene activation by affecting Stat3's ability to bind to its target sites on chromatin. Nanog overexpression or inhibition of MAPK/ERK signaling, both known to maintain mESCs in the absence of LIF, rescued Tet1 depletion, further supporting the dependence of LIF/Stat3 signaling on Tet1. These data support the conclusion that analysis of mESCs in the hours/days immediately following efficient Tet1 depletion reveals Tet1s normal physiological role in maintaining the pluripotent state that may be subject to homeostatic compensation in genetic models.
Publication Title
Acute depletion of Tet1-dependent 5-hydroxymethylcytosine levels impairs LIF/Stat3 signaling and results in loss of embryonic stem cell identity.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The positioning of nucleosomes with respect to DNA plays an important role in regulating transcription. However, nucleosome mapping has been performed for only limited genomic regions in humans. We have generated genome-wide maps of nucleosome positions in both resting and activated human CD4+ T cells by direct sequencing of nucleosome ends using the Solexa high-throughput sequencing technique.
Publication Title
Dynamic regulation of nucleosome positioning in the human genome.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
Description
Even though T-cell receptor (TCR) stimulation together with co-stimulation is sufficient for the activation of both na誰ve and memory T cells, the memory cells are capable of producing lineage specific cytokines much more rapidly than the na誰ve cells. The mechanisms behind this rapid recall response of the memory cells are still not completely understood. Here, we performed epigenetic profiling of human resting na誰ve, central and effector memory T cells using ChIP-Seq and found that unlike the na誰ve cells, the regulatory elements of the cytokine genes in the memory T cells are marked by activating histone modifications even in the resting state. Therefore, the ability to induce expression of rapid recall genes upon activation is associated with the deposition of positive histone modifications during memory T cell differentiation. We propose a model of T cell memory, in which immunological memory state is encoded epigenetically, through poising and transcriptional memory. Overall design: Chromatin state of resting Human Naive, Central memory (TCM) and Effector Memory (TEM) T cells was analyzed by ChIP-Seq; Gene expression in resting and activated for 40 min, 150 min and 15hrs Naive, TCM and TEM cells was analyzed by RNA-Seq
Publication Title
Rapid Recall Ability of Memory T cells is Encoded in their Epigenome.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- IlluminaHiSeq2500
Description
Alterations in chromatin modifications, including DNA methylation and histone modification patterns, have been characterized under exposure of several environmental pollutants, including nickel. As with other carcinogenic metals, the mutagenic potential of nickel compounds is low and is not well correlated with its carcinogenic effects. Nickel exposure, however, is associated with alterations in chromatin modifications and related transcriptional programs, suggesting an alternative pathway whereby nickel exposure can lead to disease. To investigate the extent to which nickel exposure disrupts chromatin patterns, we profiled several histone modifications, including H3K4me3, H3K9ac, H3K27me3 and H3K9me2 as well as the insulator binding protein CTCF and the transcriptomes of control BEAS-2B cells and cells treated with nickel for 72 hours. Our results show significant alterations of the repressive histone modification H3K9me2 in nickel-exposed cells with spreading of H3K9me2 into new domains associated with gene silencing. We furthermore show that local regions of active chromatin can protect genes from nickel-induced H3K9me2 spreading. Interestingly, we show that nickel exposure selectively disrupts weaker CTCF sites, leading to spreading of H3K9me2 at these regions. These results have major implications in the understanding of how environmental carcinogens can affect chromatin dynamics and the consequences of chromatin domain disruption in disease progression. Overall design: Treat BEAS-2B cells with NiCl2 for 72 hours and compare histone modification, CTCF binding to control BEAS-2B cells to see how they regulated gene expression by RNA-seq
Publication Title
Epigenetic dysregulation by nickel through repressive chromatin domain disruption.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- IlluminaHiSeq2500
Description
Purpose: Oxygen (O2) levels in cell culture conditions is typically 2-5 fold higher than the physiological O2 levels that most tissues experience in vivo. The ambient atmospheric O2 (21%) is known to induce cell proliferation defects and cellular senescence in stem cell and primary cell cultures. Therefore, culturing these cells under lower O2 levels (2-9%) is currently a standard practice. However, the non-cancerous immortalized cells and cancer cells, which evade cellular senescence are normally cultured under 21% O2 levels and the effects of higher O2 levels on these cells are not fully understood. Methods: Gene expression (RNA seq transcriptomics) analysis of immortalized human bronchial epithelial (BEAS-2B) cells cultured at ambient 21% O2 and lower 10% O2 levels for 3 days and 3 weeks. Further the beneficial effects of cuturing cells under lower oxygen tension is evalulated Results: Our results show NF-?B/RelA mediated activation of pro-inflammatory cytokines as a major outcome of cells being cultured 21% O2. Moreover, we demonstrate increased RelA binding at the NF-?B1/RelA target gene promoters at 21% O2. Interestingly, contrary to cells cultutred at 21% O2, external stress induced by H2O2 exposure did not induce inflammatory response in cells grown at 10% O2, suggesting increased ability to handle external stress in cells cultured at lower O2 levels. Overall design: RNA Seq gene expression comparision done in replicates
Publication Title
Nuclear Factor κB1/RelA Mediates Inflammation in Human Lung Epithelial Cells at Atmospheric Oxygen Levels.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 5 Downloadable Samples
- Illumina HiSeq 2000
Description
The Drosophila insulator-binding proteins (IBPs) dCTCF/Beaf32 mark the physical borders of chromosomal domains involving co-factors that participate in long-range interactions. Chromosomal borders are further enriched in specific histone modifications yet the implication of histone modifiers and nucleosome dynamics remains largely unknown in such context. Here, we show that IBP depletion impairs nucleosome dynamics over genes flanked by their binding sites. Biochemical purification identifies a key histone methyltransferase of H3K36, NSD/dMes-4, as a novel co-factor of IBPs involved in chromatin accessibility, which specifically co-regulates hundreds of genes flanked by Beaf32/dCTCF. dMes-4 presets chromatin before the recruitment of transcriptional activators including DREF that triggers Set2/Hypb-mediated H3K36me3, RNA splicing and nucleosome positioning. Our results unveil a model for how IBPs regulate gene expression and nucleosome dynamics through NSD/dMes-4, which may contribute to regulate H3K27me3 spreading. Together, our data suggest a division of labor for how IBPs may dynamically regulate chromatin organization depending on distinct co-factors. Overall design: mRNA profiles of Beaf32-depleted or Wild-Type control Drosophila S2 cells by RNASeq (Illumina)
Publication Title
Insulators recruit histone methyltransferase dMes4 to regulate chromatin of flanking genes.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
To better elucidate epigenetic mechanisms that correlate with the dynamic gene expression program observed after T cell activation, we investigated the genomic landscape of histone modifications in antigen-experienced CD8+ T cells. Using a ChIP-Seq approach coupled with global gene expression profiling, we generated genome-wide histone H3 lysine 4 (H3K4me3) and H3 lysine 27 (H3K27me3) trimethylation maps in distinct subsets of CD8+ T cells-nave, stem cell memory, central memory, and effector memory-to gain insight into how histone architecture is remodeled during the differentiation of activated T cells. We show that H3K4me3 histone modifications are associated with activation of genes, while H3K27me3 is negatively correlated with gene expression at canonical loci and enhancers regions associated with T cell metabolism, effector function, and memory. Our results also reveal histone modifications and gene expression signatures that distinguish the recently identified stem cell memory T cell from other antigen-experienced CD8+ T cell subsets. Taken together, our results suggest that antigen-experienced T cells may undergo chromatin remodeling in a progressive fashion that may have implications for our understanding of peripheral T cell ontogeny and the formation of immunological memory.
Publication Title
Lineage relationship of CD8(+) T cell subsets is revealed by progressive changes in the epigenetic landscape.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression profiling has been performed on astrocytes isolated using laser capture microdissection (LCM) from multiple sclerosis normal appearing white matter (NAWM) and control WM to identify whether specific glial changes exist in NAWM which contribute to lesion development or prevent disease progression
Publication Title
Gene expression profiling of the astrocyte transcriptome in multiple sclerosis normal appearing white matter reveals a neuroprotective role.
Sample Metadata Fields
Specimen part, Disease
View Samples