H3K27me3 ChIP-seq profiling in MCF7 cell lines under hypoxia
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE61740 | GEO | 2014/09/26
SECONDARY ACCESSION(S): PRJNA262005
REPOSITORIES: GEO
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Project description:Purpose: Study hypoxia induced changes in genome-wide H3K27me3 occupancy Methods: Using the MCF7 breast epithelial adenocarcinoma cell line as a model, we studied epigenomic reprogramming as a function of fluctuating oxygen tension. To this end, we combined chromatin-immunoprecipitation and deep-sequencing analysis to identify H3K27me3-marks in MCF7 cells subjected to changes in oxygenation (i.e. acute hypoxia, chronic hypoxia). Results: H3K27me3-marks showed a rapid global increase at specific sites throughout the genome under hypoxia, both genic and inter-genic. Conclusions: Our data show that oxygen availability dynamically regulates the epigenetic state of the genome. Genome-wide H3K27me3-mark profiles were generated by combining ChIP analysis with deep sequencing using Illumina GAIIx.
2014-09-26 | E-GEOD-61740 | biostudies-arrayexpress
Project description:Purpose: Study hypoxia and reoxygenation induced changes in genome-wide H3K4me3 and H3K27me3 occupancy Methods: Using the MCF7 breast epithelial adenocarcinoma cell line as a model, we studied epigenomic reprogramming as a function of fluctuating oxygen tension. To this end, we combined chromatin-immunoprecipitation and deep-sequencing analysis to identify H3K4me3-marks and H3K27me3-marks in MCF7 cells subjected to changes in oxygenation (i.e. acute hypoxia, chronic hypoxia, reoxygenation). Results: H3K4me3 and H3K27me3-marks showed a rapid global increase at specific sites throughout the genome under hypoxia, both genic and inter-genic, that was partly restored upon reoxygenation. Conclusions: Our data show that oxygen availability dynamically regulates the epigenetic state of the genome.
2016-11-01 | GSE71030 | GEO
Project description:Purpose: Study hypoxia and reoxygenation induced changes in genome-wide gene expression Methods: Using the MCF7 breast epithelial adenocarcinoma cell line as a model, we studied epigenomic reprogramming as a function of fluctuating oxygen tension. To this end, we performed a transcriptomics analysis in MCF7 cells subjected to changes in oxygenation (i.e. acute hypoxia, chronic hypoxia, reoxygenation). Results: Global downregulation upon hypoxia; partial restore on reoxygenation. Conclusions: Our data show that oxygen availability dynamically regulates gene transcription.
2016-11-01 | GSE70805 | GEO
Project description:This study compares response to hypoxia in muscle between 2 hypoxia tolerant species of Spalax ehrenbergi, blind subterranean mole rat . The blind subterranean mole rat (Spalax ehrenbergi superspecies) is an excellent model of hypoxic tolerance, living underground and exposed to fluctuating O2 and CO2 levels. Unique structural and functional adaptations of the cardiovascular and respiratory systems allow survival at severely reduced oxygen tension. In this study we have compared expression profiles of muscle tissue between two hypoxia tolerant species of Spalax ehrengergi at normoxic (21%) and hypoxic (3%) levels of oxygen concentration by cross species hybridization using a mouse cDNA array containing 15,000 gene elements. Results uncover numerous genes involved in angiogenesis, apoptosis, and oxidative stress and responding in a species specific manner to hypoxia. Among the most striking, cardiac ankyrin repeat protein (Carp) and activating transcription factor 3 (Atf3), LIM and cysteine-rich domains 1 (Lmcd1) and syndecan 2 (Sdc2). These results support the hypothesis that Spalax is variably adapted to fluctuating oxygen tension. Differences may involve very specific metabolic pathways and functional adaptations at the structural and molecular levels. Elucidation of the natural variation and evolutionary changes under hypoxia within this superspecies may have biomedical applications in ischemic syndromes and cancer. Keywords: hypoxia, Spalax, cDNA microarray
2006-07-14 | GSE3763 | GEO
Project description:This 58 arrays are the basis of our hypoxia story published in PLoS Medicine. The cell type, oxygen tension and time points are indicated.
2006-06-06 | E-SMDB-3611 | biostudies-arrayexpress
Project description:Adipose tissue is a plentiful and easily accessible source of mesenchymal stem cells that have been shown to be multi potent and possibly have immuno suppressive capacity(Zuk, Zhu et al. 2002; McIntosh, Zvonic et al. 2006; Prichard, Reichert et al. 2008). Several studies have identified hypoxia and the molecular effector of reduced oxygen tension, HIF1α to be essential in the differentiation processes, stem cell proliferation and survival as well as in maintenance of stem cell characteristics (Lennon, Edmison et al. 2001; Goda, Ryan et al. 2003; Wang, Fermor et al. 2005; Lin, Lee et al. 2006; Malladi, Xu et al. 2007; Ohnishi, Yasuda et al. 2007). The fact that oxygen has a central role in cell development and metabolism makes the regulation of oxygen tension a valuable tool in the attempt of exploiting stem cells to their full potential. In the current study we investigate the transcriptional changes caused by two weeks of monolayer hypoxic expansion of human adipose tissue derived stem cells (ASCs). Application of the XVivo hypoxic workstation (BioSpherix, Redfield, NY) made it possible to conduct the expansion of six ASC lines at four different hypoxic conditions in parallel covering the range from mild (15% oxygen) to full hypoxic (1% oxygen) conditions. In this comprehensive investigation the Illumina bead microarray platform was employed to give a profound and new insight in the molecular changes effectuated by hypoxic expansion. The findings of this study demonstrate the significance of biologic variation in the transcriptional response to mild hypoxic expansion and display evidence that full hypoxic growth conditions at 1% oxygen tension selects for a more prolific cell population of reduced chondrogenic potential. Keywords: hypoxia response To investigate the transcriptional response to hypoxia, adipose tissue derived stem cells (ASCs) from six female individuals were cultured for 14 days at different oxygen tensions (ambient, 15%, 10%, 5% and 1%). Gene expression levels at each oxygen tension were compared to ambient conditions (Ambient oxygen tension) using Illumina Human-6 v2.0 microarrays.
2010-06-25 | E-GEOD-12884 | biostudies-arrayexpress
Project description:The mechanisms by which the placenta adapts to exogenous stimuli to create a stable and healthy environment for the growing fetus are not well known. Low oxygen tension and sub-optimal vitamin D levels influence placental function and both are associated with preeclampsia, a condition associated with altered development of placental trophoblast. We hypothesized that oxygen tension, vitamin D levels, or both affect villous trophoblast by modulation of gene expression through DNA methylation. To test this we used the Illumina Infinium Human Methylation 450 BeadChip array to compare the DNA methylation profile of primary cultures of human cytotrophoblasts and syncytiotrophoblasts under three oxygen tensions and three vitamin D levels. We found no effect on global DNA methylation by either treatment, but a limited set of loci became hypermethylated in cytotrophoblasts exposed for 24 hours to 1% oxygen, as compared to the same cells exposed to 8% or 20% oxygen. Vitamin D levels had no detectable effect on methylation profiles in either trophoblast type. Hypermethylation with low oxygen tension was independently confirmed by bisulfite-pyrosequencing in a subset of functionally important genes including CP, ITGA5, SOD2, XDH and ZNF2. Intriguingly, 70 out of the 147 hypoxia-associated CpGs, overlapped with CpG sites that become hypomethylated upon differentiation of cytotrophoblasts into syncytiotrophoblasts. Furthermore, the preponderance of altered sites was located at AP-1 binding sites. We suggest that AP-1 expression is triggered by hypoxia and interacts with DNA methyltransferases (DNMTs) to target methylation at specific sites in the genome, thus causing suppression of the associated genes that are responsible for differentiation of villous cytotrophoblast to syncytiotrophoblast. RNA from cytotrophoblast from 2 placentas exposed to 3 different conditions of hypoxia (1%,8%,20%) and treated with 3 levels of vitamin D were run on the Illumina HT-12v4 Expression Array
2013-01-18 | E-GEOD-41331 | biostudies-arrayexpress
Project description:The mechanisms by which the placenta adapts to exogenous stimuli to create a stable and healthy environment for the growing fetus are not well known. Low oxygen tension and sub-optimal vitamin D levels influence placental function and both are associated with preeclampsia, a condition associated with altered development of placental trophoblast. We hypothesized that oxygen tension, vitamin D levels, or both affect villous trophoblast by modulation of gene expression through DNA methylation. To test this we used the Illumina Infinium Human Methylation 450 BeadChip array to compare the DNA methylation profile of primary cultures of human cytotrophoblasts and syncytiotrophoblasts under three oxygen tensions and three vitamin D levels. We found no effect on global DNA methylation by either treatment, but a limited set of loci became hypermethylated in cytotrophoblasts exposed for 24 hours to 1% oxygen, as compared to the same cells exposed to 8% or 20% oxygen. Vitamin D levels had no detectable effect on methylation profiles in either trophoblast type. Hypermethylation with low oxygen tension was independently confirmed by bisulfite-pyrosequencing in a subset of functionally important genes including CP, ITGA5, SOD2, XDH and ZNF2. Intriguingly, 70 out of the 147 hypoxia-associated CpGs, overlapped with CpG sites that become hypomethylated upon differentiation of cytotrophoblasts into syncytiotrophoblasts. Furthermore, the preponderance of altered sites was located at AP-1 binding sites. We suggest that AP-1 expression is triggered by hypoxia and interacts with DNA methyltransferases (DNMTs) to target methylation at specific sites in the genome, thus causing suppression of the associated genes that are responsible for differentiation of villous cytotrophoblast to syncytiotrophoblast. DNA from 2 cell types from 5 placentas exposed to 3 different conditions of hypoxia (1%,8%,20%) and treated with 3 levels of vitamin D were bisulfite converted and run on the Illumina HumanMethylation450 BeadChip
2013-01-18 | E-GEOD-41336 | biostudies-arrayexpress
Project description:Hypoxia augments human embryonic stem cell self-renewal via hypoxia-inducible factor 2M-NM-1 (HIF2M-NM-1) activated OCT4 (POU5F1) transcription. Hypoxia also increases the efficiency of reprogramming differentiated cells to a pluripotent-like state. Combined, these findings suggest that low oxygen (O2) tension would impair the purposeful differentiation of pluripotent stem cells. Here, we show that low O2 tension and HIF activity instead promotes appropriate hESC differentiation. Through gain and loss of function studies, we implicate O2 tension as a modifier of a key cell fate decision, namely whether neural progenitors differentiate towards neurons or glia. Furthermore, our data show that even transient changes in O2 concentration can affect cell fate through HIF by regulating the activity of MYC, a regulator of LIN28/let-7 that is critical for fate decisions in the neural lineage. We also identify key small molecules that can take advantage of this pathway to quickly and efficiently promote the development of mature cell types. We used microarrays to detail the global gene expression of human neural progenitor cells (NPC) cultured in physiological (2%) oxygen tension. By comparing NPCs with activated Hypoxia inducible factor (HIF) activity (DFX treatment) and NPCs with diminished HIF activity (HIF1M-NM-2 knockdown), we identified genes that are important for NPC fate decision under physiological oxygen concentration. We also used microarrays to obtain a global gene expression profiling during embryoid bodies formation using ES cells with diminished HIF activity. In HIF activation experiments, two ES lines and one iPS line-derived NPC were used, with or without DFX treatment for 5 days. In HIF1M-NM-2 knockdown experiments, NPCs were derived from either shHIF1M-NM-2 or control ES lines. In embryoid body formation experiments, day0 (ES stage) and day6 EBs were generated from either shHIF1M-NM-2 or control ES lines in 2% oxygen.
2014-09-30 | E-GEOD-61842 | biostudies-arrayexpress
Project description:MicroRNAs are small regulatory RNAs that post-transcriptionally control gene expression. Reduced expression of DICER, the enzyme involved in microRNA processing, is frequently observed in cancer and is associated with poor clinical outcome in various malignancies. Yet the underlying mechanisms are not well understood. Here, we identify tumor hypoxia as a regulator of DICER expression in large cohorts of breast cancer patients. We show that DICER expression is suppressed by hypoxia through an epigenetic mechanism that involves inhibition of oxygen-dependent H3K27me3 demethylases KDM6A/B and results in silencing of the DICER promoter. Subsequently, reduced miRNA processing leads to derepression of the miR-200 target ZEB1, stimulates the epithelial to mesenchymal transition and ultimately results in the acquisition of stem cell phenotypes in human mammary epithelial cells. Our study uncovers a previously unknown relationship between oxygen-sensitive epigenetic regulators, miRNA biogenesis and tumor stem cell phenotypes that may underlie poor outcome in breast cancer. miRNA profiling of MCF7 cells in normal or hypoxic conditions or after DICER knockdown in MCF7 cells.
2014-09-30 | E-GEOD-61720 | biostudies-arrayexpress