An epigenetic regulatory loop of master regulator transcription factors/PPARG/fatty-acid synthesis in promoting esophageal adenocarcinoma
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ABSTRACT:
PROVIDER: PRJNA599174 | ENA |
REPOSITORIES: ENA
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Project description:We profiled esophageal adenocarcinoma cell lines with chromatin immunoprecipitation sequencing (ChIP-Seq). Mathematically modeling was performed to establish (super)-enhancers landscapes and inter-connected transcriptional circuitry formed by master TFs. Coregulation and cooperation between master TFs was investigated by ChIP-Seq, RNA-Seq, 4C-Seq and luciferase assay. Biological functions of candidate factors were evaluated by measuring cell proliferation, colony formation, cell apoptosis and xenograft growth. Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. Here, we aim to compare of Eso26 or OE33 cells knock down PPARG with siRNA and control transcriptome profiling (RNA-seq) to microarray and quantitative reverse transcription polymerase chain reaction (qRT–PCR) methods and to evaluate protocols for optimal high-throughput data analysis. We also report the application of ChIP sequencing technology for studying master transcription factor (PPARG) in human esophageal adenocarcinoma cancer cell lines (Eso26 and OE33).
2020-06-06 | GSE143195 | GEO
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| S-EPMC8026506 | biostudies-literature
Project description:We find that Pparg is a master regulator of cell specification during urothelial homeostasis, driving a luminal differentiation program via retinoid signaling. Interestingly, expression of activated Pparg in basal cells only drives tumor formation when they are in an activated state, that are in an activated state, induces formation of luminal tumors with papillary morphology, Expression of an activated form of Pparg induces basal cells at homeostasis, to differentiate directly into luminal cells. In a BBN mouse model which produces basal subtypes tumors in wild type animals, activated Pparg drives formation of luminal tumors, suggesting that this transcription factor is a master regulator of luminal differentiation, as has been suggested from in vitro studies.
2021-09-22 | GSE172656 | GEO
Project description:Robust identification of placental PPARg target genes via mutliple PPARg-dependence criteria. Integration of differential expression data from Pparg-null, Rxra-null, Med1-nul and Ncoa6-null placentas and from WT and Pparg-null Trophoblast stem cells (TSC) differentiated for 2 or 4 days in the presence or absence of the PPARg agonist Rosiglitazone (Rosi).
2012-07-10 | GSE39233 | GEO
Project description:Robust identification of placental PPARg target genes via mutliple PPARg-dependence criteria. Integration of differential expression data from Pparg-null, Rxra-null, Med1-nul and Ncoa6-null placentas and from WT and Pparg-null Trophoblast stem cells (TSC) differentiated for 2 or 4 days in the presence or absence of the PPARg agonist Rosiglitazone (Rosi). [Placentas] Three pools of three WT placentas, each vs a litter-matched pool of three Pparg-null placentas Three pools of three WT placentas, each vs a litter-matched pool of three Rxra-null placentas Three pools of three WT placentas, each vs a litter-matched pool of three Med1-null placentas Three pools of three WT placentas, each vs a litter-matched pool of three Ncoa6-null placentas [Trophoblast stem cells (TSC)] Three independent WT TSC lines differentiated for two and four days in the presence or absence of Rosi vs two independent Pparg-null TSC lines differntiated for the same durations in the presence of Rosi
2012-07-09 | E-GEOD-39233 | biostudies-arrayexpress
Project description:Conditional macrophage-specific PPARg knockout mice were generated on C57Bl/6 background by breeding PPARg fl/- (one allele is floxed, the other is null) and lysozyme Cre transgenic mice. PPARg and IL-4 signaling was analyzed on bone marrow-derived macrophages. Bone marrow of 3 mice per group was isolated and differentiated to macrophages with M-CSF (20 ng/ml). 20 ng/ml IL-4 was used to induce alternative macrophage activation and 1 uM Rosiglitazone (RSG) was used to activate PPARg. From each mouse 4 samples were generated: 1. M-CSF, 2. M-CSF+RSG, 3. IL-4 and 4. IL-4+RSG. All compounds were added throughout the whole differentiation process, and fresh media was added every other day. Control cells were treated with vehicle (DMSO:ethanol). After 10 days, RNA was isolated and gene expression profiles were analyzed using Mouse Genome 430 2.0 microarrays from Affymetrix. 3 PPARg +/- LysCre and 3 PPARg fl/- LysCre mice were used to isolate bone marrow and from each macrophages were differentiated with or without IL-4 and simultaneously treated with vehicle or RSG. Altogether we analyzed 24 samples with 3 biological replicates as below.
2010-11-18 | E-GEOD-25123 | biostudies-arrayexpress
Project description:PPARG interactome datasets containing (1) Flag-PPARG AP-MS, identifying MRE11, RAD50 and NBS1 as novel interactors, (2) tandem-IP (in solution and silver fragments) of PPARG-Strep and Flag-NBS1, which identifies PPARG interaction with UBR5 (3) tandem-IP (same as 2) with BS3 cross-linking illustrates the binding interface between PPARG and NBS1.
These mass spec data and other biochemical data demonstrate PPARG novel roles in promoting DNA damage response and repair, by activating the ATM pathway.
2018-12-18 | MSV000083257 | MassIVE
Project description:Conditional macrophage-specific PPARg knockout mice were generated on C57Bl/6 background by breeding PPARg fl/- (one allele is floxed, the other is null) and lysozyme Cre transgenic mice. PPARg and IL-4 signaling was analyzed on bone marrow-derived macrophages. Bone marrow of 3 mice per group was isolated and differentiated to macrophages with M-CSF (20 ng/ml). 20 ng/ml IL-4 was used to induce alternative macrophage activation and 1 uM Rosiglitazone (RSG) was used to activate PPARg. From each mouse 4 samples were generated: 1. M-CSF, 2. M-CSF+RSG, 3. IL-4 and 4. IL-4+RSG. All compounds were added throughout the whole differentiation process, and fresh media was added every other day. Control cells were treated with vehicle (DMSO:ethanol). After 10 days, RNA was isolated and gene expression profiles were analyzed using Mouse Genome 430 2.0 microarrays from Affymetrix.
2010-11-18 | GSE25123 | GEO
Project description:The discreteness of cell fates is an inherent and fundamental feature of multicellular organisms. Here we show that cross-antagonistic mechanisms of actions of MyoD and PPARg, which are the master regulators of muscle and adipose differentiation, respectively, confer the robustness to the integrity of cell differentiation. Simultaneous expression of MyoD and PPARg in mesenchymal stem/stromal cells led to the generation of a mixture of multinucleated myotubes and lipid-filled adipocytes. Interestingly, hybrid cells, i.e., lipid-filled myotubes, were not generated, suggesting that these differentiation programs are mutually exclusive. Mechanistically, while exogenously expressed MyoD was rapidly degraded in adipocytes through ubiquitin-proteasome pathways, exogenously expressed PPARg was not down-regulated in myotubes. In PPARg-expressing myotubes, PPARg-dependent histone hyperacetylation was inhibited in a subset of adipogenic gene loci, including that of C/EBPa, an essential effector of PPARg. Thus, the cross-repressive interactions between MyoD- and PPARg-induced differentiation programs ensure the discrete cell fate decisions. To gain insights into the mechanisms by which adipogenic differentiation is inhibited in PPARg-expressing myotubes, we performed microarray analysis to compare gene expression profiles of the myotube-enriched (M) fraction and the adipocyte-enriched (A) fraction. M fraction and A fraction were obtained by fractionating a mixture of myotubes and adipocytes, which was generated by simultaneous expression of MyoD and PPARg, according to cell size. Microarray analysis was performed using mRNA isolated from C3H10T1/2 cells. We used five samples: non-infected cells, control lentivirus-infected cells, HA-PPARg-infected cells, and cells co-infected with Myc-MyoD and HA-PPARg and then fractionated accroding to cell size (M-fraction and A-fraction). Total RNA was prepared using the RNeasy Mini Kit (Qiagen) according to the manufacturer’s instruction. Other procedures including hybridization to the Mouse Gene 1.0 ST array (Affymetrix) were performed according to Affymetrix protocols. The affymetrix outputs (CEL files) were imported into GeneSpring GX 11.0.2 (Agilent Technologies) microarray analysis software for presentation of the expression profiles. Probe intensities were normalized, and expression signals of all genes (probe sets) were calculated using RMA (robust multi-array analysis, as implemented in GeneSpring GX).
2014-05-08 | E-GEOD-56082 | biostudies-arrayexpress
Project description:The discreteness of cell fates is an inherent and fundamental feature of multicellular organisms. Here we show that cross-antagonistic mechanisms of actions of MyoD and PPARg, which are the master regulators of muscle and adipose differentiation, respectively, confer the robustness to the integrity of cell differentiation. Simultaneous expression of MyoD and PPARg in mesenchymal stem/stromal cells led to the generation of a mixture of multinucleated myotubes and lipid-filled adipocytes. Interestingly, hybrid cells, i.e., lipid-filled myotubes, were not generated, suggesting that these differentiation programs are mutually exclusive. Mechanistically, while exogenously expressed MyoD was rapidly degraded in adipocytes through ubiquitin-proteasome pathways, exogenously expressed PPARg was not down-regulated in myotubes. In PPARg-expressing myotubes, PPARg-dependent histone hyperacetylation was inhibited in a subset of adipogenic gene loci, including that of C/EBPa, an essential effector of PPARg. Thus, the cross-repressive interactions between MyoD- and PPARg-induced differentiation programs ensure the discrete cell fate decisions. To gain insights into the mechanisms by which adipogenic differentiation is inhibited in PPARg-expressing myotubes, we performed microarray analysis to compare gene expression profiles of the myotube-enriched (M) fraction and the adipocyte-enriched (A) fraction. M fraction and A fraction were obtained by fractionating a mixture of myotubes and adipocytes, which was generated by simultaneous expression of MyoD and PPARg, according to cell size.
2014-05-08 | GSE56082 | GEO