This SuperSeries is composed of the SubSeries listed below.
PPARG binding landscapes in macrophages suggest a genome-wide contribution of PU.1 to divergent PPARG binding in human and mouse.
Specimen part, Cell line, Treatment
View SamplesGenome-wide comparisons of transcription factor binding sites in different species allow for a direct evaluation of the evolutionary constraints that shape transcription factor binding landscapes. To gain insights into the evolution of the PPARg-dependent transcriptional network we obtained binding data for PPARg, RXR and PU.1 in human macrophages and compared the profiles to matching data from mouse macrophages. We found that PPARg binding was highly divergent and only 5% of the PPARg bound regions were occupied in both species. Despite the low conservation of PPARg binding sites, conserved PPARg target genes contribute more than 30% to the functional target genes identified in human macrophages. In addition conserved target genes are strongly enriched for lipid metabolic functions. We detected the lineage-specification factor PU.1 at the majority of human PPARg binding sites. This confirmed the juxtaposed binding configuration found in mouse macrophages and demonstrated the preservation of tissue-specific adjacent PPARg-Pu.1 binding in the absence of individual binding site conservation. Finally, based on this of PPARg and PU.1 binding between human and mouse we suggest a mechanism by which PU.1 facilitates PPARg binding site turnover in macrophages.
PPARG binding landscapes in macrophages suggest a genome-wide contribution of PU.1 to divergent PPARG binding in human and mouse.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transposable elements have rewired the core regulatory network of human embryonic stem cells.
Specimen part, Disease, Cell line, Time
View SamplesWe studied the genomic locations of three key regulatory proteins (OCT4, NANOG and CTCF) in human and mouse embryonic stem (ES) cells [see Series GSE20650]. To identify the conserved and unique human OCT4 targets, we performed an OCT4 RNAi knock-down experiment. We find that species-specific transposable elements have profoundly altered the transcriptional circuitry of pluripotent stem cells.
Transposable elements have rewired the core regulatory network of human embryonic stem cells.
Specimen part, Disease, Cell line, Time
View SamplesWe studied the variations of mRNA amounts after Flag-EVI1, Flag-EVI1324, or Flag expression in HeLa cells. Despites EVI1 discovery in 1988, its recognized role as a dominant oncogene in myeloid leukemia and more recently in epithelial cancers, only a few target genes were known and it was not clear why EVI1 was involved in cancer progression. Here we obtained the genomic binding occupancy and expression data for EVI1 in human cells. We identified numerous EVI1 target cancer genes and genes controlling cell migration and adhesion. Moreover, we characterized a transcriptional cooperation between AP1 and EVI1 that regulated proliferation and adhesion through a feed-forward loop. This study provides human genome-wide mapping and expression analyses for EVI1 that will be useful for the research community.
Functional features of EVI1 and EVI1Δ324 isoforms of MECOM gene in genome-wide transcription regulation and oncogenicity.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The PGC-1α/ERRα Axis Represses One-Carbon Metabolism and Promotes Sensitivity to Anti-folate Therapy in Breast Cancer.
Specimen part, Cell line
View SamplesReprogramming of cellular metabolism plays a central role in fuelling malignant transformation, and AMPK as well as the PGC-1/ERR axis are key regulators of this process. Intersection of gene expression and binding event datasets in breast cancer cells shows that activation of AMPK significantly increases the expression of PGC-1/ERR and promotes the binding of ERR to its cognate sites. Unexpectedly, the data also reveal that ERR, in concert with PGC-1, negatively regulates the expression of several one-carbon metabolism genes resulting in substantial perturbations in purine biosynthesis. This PGC-1/ERR-mediated repression of one-carbon metabolism promotes the sensitivity of breast cancer cells and tumors to the anti-folate drug methotrexate. These data implicate the PGC-1/ERR axis as a core regulatory node of folate cycle metabolism and further suggest that activators of AMPK could be used to modulate this pathway in cancer.
The PGC-1α/ERRα Axis Represses One-Carbon Metabolism and Promotes Sensitivity to Anti-folate Therapy in Breast Cancer.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Ecotopic viral integration site 1 (EVI1) regulates multiple cellular processes important for cancer and is a synergistic partner for FOS protein in invasive tumors.
Specimen part, Cell line
View SamplesWe studied the variations of mRNA amounts after Evi1 knockdown or Flag-Evi1 overexpression in SKOV-3 cells.
Ecotopic viral integration site 1 (EVI1) regulates multiple cellular processes important for cancer and is a synergistic partner for FOS protein in invasive tumors.
Cell line
View SamplesWe studied the variations of mRNA amounts after Flag-EVI1 or Flag expression in HeLa cells.
Ecotopic viral integration site 1 (EVI1) regulates multiple cellular processes important for cancer and is a synergistic partner for FOS protein in invasive tumors.
Cell line
View Samples