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GSE56539
Homo sapiens
14 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Impact of human MLL/COMPASS and polycomb complexes on the DNA methylome.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The association of DNA CpG methylation (or its absence) with occupancy of histone post translational modifications has hinted at an underlying crosstalk between histone marks and DNA methylation in patterning the human methylome, an idea supported by corresponding alterations to both histone marks and DNA methylation during malignant transformation. This study investigated the framework by which histone marks influence DNA methylation. Using RNAi in a human pluripotent embryonic carcinoma cell line we depleted essential components of the histone modifying complexes that establish the posttranslational modifications H3K4me3, H3K27me3, and H2AK119ub, and we assayed the impact of the subsequent loss of these marks on the DNA methylome. Absence of H2AK119ub resulted predominantly in hypomethylation across the genome. Removal of H3K4me3 or, surprisingly, H3K27me3 caused CpG island hypermethylation at a subset of loci. Intriguingly, many promoters were co-regulated by all three histone marks, becoming hypermethylated with loss of H3K4me3 or H3K27me3 and becoming hypomethylated with depletion of H2AK119ub, and many of these co-regulated loci were among those that are commonly, aberrantly hypermethylated in cancer.
Publication Title
Impact of human MLL/COMPASS and polycomb complexes on the DNA methylome.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Distinct and overlapping control of 5-methylcytosine and 5-hydroxymethylcytosine by the TET proteins in human cancer cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The TET family of dioxygenases catalyze conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), but their involvement in establishing normal 5mC patterns during mammalian development and their contributions to aberrant control of 5mC during cellular transformation remains largely unknown. We depleted TET1, TET2, and TET3 by siRNA in a pluripotent embryonic carcinoma cell model and examined the impact on genome-wide 5mC and 5hmC patterns. TET1 depletion yielded widespread reduction of 5hmC, while depletion of TET2 and TET3 reduced 5hmC at a subset of TET1 targets suggesting functional co-dependence. TET2 or TET3-depletion also caused increased 5hmC, suggesting they play a major role in 5hmC removal. All TETs prevent hypermethylation throughout the genome, a finding dramatically illustrated in CpG island shores, where TET depletion resulted in prolific hypermethylation. Surprisingly, TETs also promote methylation, as hypomethylation was associated with 5hmC reduction. TET function was highly specific to chromatin environment: 5hmC maintenance by all TETs occurred at polycomb-marked chromatin and genes expressed at moderate levels; 5hmC removal by TET2 is associated with highly transcribed genes enriched for H3K4me3 and H3K36me3. Importantly, genes prone to hypermethylation in cancer become depleted of 5hmC with TET deficiency, suggesting the TETs normally promote 5hmC at these loci, and all three TETs are required for 5hmC enrichment at enhancers, a condition necessary for expression of adjacent genes. These results provide novel insight into the division of labor among TET proteins and reveal an important connection of TET activity with chromatin landscape and gene expression.
Publication Title
Distinct and overlapping control of 5-methylcytosine and 5-hydroxymethylcytosine by the TET proteins in human cancer cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 250 Downloadable Samples
Illumina HiSeq 2500, Ion Torrent Proton
Description
The goal of this study is to compare transcriptional profiles of regulatory T cells and conventional CD4 T cells in human breast cancer to regulatory T cells and conventional CD4 T cells in normal breast parenchyma and in peripheral blood. Overall design: RNA sequencing of 2 different cell types in 3 different tissues
Publication Title
Regulatory T Cells Exhibit Distinct Features in Human Breast Cancer.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 28 Downloadable Samples
- Illumina HiSeq 2000
Description
Thymic Treg cells, mature non-Treg CD4+ single positive thymocytes, peripheral (spleen) resting and activated Treg cells were sorted from Foxp3-gfp reporter (wid type, WT) mice or Foxp3 enhancer CNS3 knockout (KO, carrying the same GFP reporter) mice. Total RNA was extracted and used for RNA sequencing to assess gene expression profiles. Overall design: Two 6-8 week old littermates of male Foxp3-gfp and Foxp3?CNS3-gfp mice were used to sort Treg cells and conventional CD4+ T cells. Lymphocyte preparation and electronic sorting were performed at the same time. RNA extraction, SMART amplification, library preparation were conducted in parallel.
Publication Title
A mechanism for expansion of regulatory T-cell repertoire and its role in self-tolerance.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Primary neonatal cardiomyocytes treated with human cardiotrophin 1 (hCT1) or control (Ctrl) for 24 hours
Publication Title
Cardiotrophin 1 stimulates beneficial myogenic and vascular remodeling of the heart.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- IlluminaHiSeq2500
Description
This study was aimed at understanding the genome-wide binding and regulatory role of the DAXX transcriptional repressor, recently implicated in PCa. ChIP-Seq analysis of genome-wide distribution of DAXX in PC3 cells revealed over 59,000 DAXX binding sites, found at regulatory enhancers and promoters. ChIP-Seq analysis of DNA methyltransferase 1 (DNMT1), which is a key epigenetic partner for DAXX repression, revealed that DNMT1 binding was restricted to a small number of DAXX sites. DNMT1 and DAXX bound close to transcriptional activator motifs. DNMT1 sites were found to be dependent on DAXX for recruitment by analyzing DNMT1 ChIP-Seq following DAXX knockdown (K/D), corroborating previous findings that DAXX recruits DNMT1 to repress its target genes. Massively parallel RNA sequencing (RNA-Seq) was used to compare the transcriptomes of WT and DAXX K/D PC3 cells. Genes induced by DAXX K/D included those involved in autophagy, and DAXX ChIP-Seq peaks were found close to the transcription start sites (TSS) of autophagy genes, implying they are more likely to be regulated by DAXX. Overall design: Determine changes in gene expression levels between WT and DAXX K/D prostate cancer cells by RNA-Seq (PC3 Cells).
Publication Title
The DAXX co-repressor is directly recruited to active regulatory elements genome-wide to regulate autophagy programs in a model of human prostate cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Estrogen signaling and epigenetic modifications, in particular DNA methylation, are involved in regulation of gene expression in breast cancers. Here we investigated a potential regulatory cross-talk between these two pathways by identifying their common target genes and exploring potential underlying molecular mechanisms in human MCF7 breast cancer cells. Principal Findings: Gene expression profiling revealed that the expression of approximately 150 genes was influenced by both 17-estradiol (E2) and a hypomethylating agent 5-aza-2-deoxycytidine (DAC). Based on gene ontology (GO), CpG island prediction analysis and previously reported estrogen receptor (ER) binding regions, we selected six genes for further analysis (BTG3, FHL2, PMAIP1, BTG2, CDKN1A and TGFB2). GO analysis suggests that these genes are involved in intracellular signaling cascades, regulation of cell proliferation and apoptosis, while CpG island prediction of promoter regions reveals that the promoters of these genes contain at least one CpG island. Using chromatin immunoprecipitation, we show that ER is recruited to CpG islands in promoters, but neither in an E2- nor in a DAC-dependent fashion. DAC treatment reactivates the expression of all selected genes although only the promoters of BTG3 and FHL2 genes are methylated, with E2 treatment showing no effect on the methylation status of these promoters. Conclusions: We identified a set of genes regulated by both estrogen signaling and DNA methylation. However, our data does not support a direct molecular interplay of mediators of estrogen and epigenetic signaling at promoters of regulated genes.
Publication Title
Global identification of genes regulated by estrogen signaling and demethylation in MCF-7 breast cancer cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In order to confirm the role of fatty acid -oxidation in Src regulation, we performed gene expression analysis in MDA231 cells from in vivo model treated with ETX or knockdown of CPT1 or CPT2 using shRNA. As expected, inhibition of -oxidation showed a gene expression pattern that is opposite to the published Src regulated gene pattern. The known Src up-regulated genes are down-regulated and Src down-regulated genes are up-regulated in -oxidation inhibited cells. Western Blotting further confirmed the gene expression pattern. Knockdown of CPT1 or CPT2 inhibited Src Y416 autophosphorylation as observed with ETX.
Publication Title
Fatty Acid Oxidation-Driven Src Links Mitochondrial Energy Reprogramming and Oncogenic Properties in Triple-Negative Breast Cancer.
Sample Metadata Fields
Cell line
View Samples