The Brakeless protein performs many important functions during Drosophila development, but how it controls gene expression is not understood. We previously showed that Brakeless can function as a transcriptional co-repressor. Here, we report transcriptional profiling of brakeless mutant embryos to identify additional target genes.
The Brakeless co-regulator can directly activate and repress transcription in early Drosophila embryos.
Specimen part
View SamplesOxidized phospoholipids are a pro-inflammatory component of minimally modified lipoproteins that get trapped in the subendothelial space of atherosclerotic plaques of large arteries. To model the response of endothelial cells in a pro-atherosclerotic enviroment we measured the expression in primary endothelial cells with and without treatment with oxidized phsopolipids from 96 genetically identical donors of anonymous origin.
Network for activation of human endothelial cells by oxidized phospholipids: a critical role of heme oxygenase 1.
Sex, Subject
View SamplesThe FAT1 gene was knocked down using 2 independent siRNAs, in immortalized human astrocytes and U87 and U251 glioma cell lines.
Recurrent somatic mutation of FAT1 in multiple human cancers leads to aberrant Wnt activation.
Cell line
View SamplesThe bromodomain and extraterminal (BET) protein Brd4 is a validated drug target in leukemia, yet its regulatory function in this disease is not well understood. Here, we show that Brd4 chromatin occupancy in acute myeloid leukemia closely correlates with the hematopoietic transcription factors (TFs) Pu.1, Fli1, Erg, C/EBPa, C/EBPß, and Myb at nucleosome-depleted enhancer and promoter regions. We provide evidence that these TFs, in conjunction with the lysine acetyltransferase activity of p300/CBP, facilitate Brd4 recruitment to their occupied sites to promote transcriptional activation. Moreover, chemical inhibition of BET bromodomains is found to suppress the functional output each hematopoietic TF, thereby interfering with essential lineage-specific transcriptional circuits in this disease. These findings reveal a chromatin-based signaling cascade comprised of hematopoietic TFs, p300/CBP, and Brd4, which supports leukemia maintenance and is suppressed by BET bromodomain inhibition. Overall design: PolyA selected RNA-Seq for drug treated or shRNA-expressing MLL-AF9 transformed acute myeloid leukemia cells (RN2)
BET Bromodomain Inhibition Suppresses the Function of Hematopoietic Transcription Factors in Acute Myeloid Leukemia.
No sample metadata fields
View SamplesGenome occupancy profiling by high throughput sequencing Overall design: PolyA selected RNA-seq for shRNA-expressing MLL-AF9 transformed acute myeloid leukemia cells (RN2)
BET Bromodomain Inhibition Releases the Mediator Complex from Select cis-Regulatory Elements.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
High Expression of Complement Component 5 (C5) at Tumor Site Associates with Superior Survival in Ewing's Sarcoma Family of Tumour Patients.
Sex, Age, Specimen part, Disease, Cell line
View SamplesPurpose: Unlike in most adult-onset cancers, an association between typical paediatric neoplasms and inflammatory triggers is rare. We studied whether immune system related genes are activated and have prognostic significance in Ewing sarcoma family of tumours (ESFT). Experimental design: Data-analysis was performed on gene expression profiles of 44 ESFT patient, 11 ESFT cell line, and 18 normal muscle tissue samples. 238 inflammation related genes were selected based on literature and a macrophage gene expression signature was derived from SymAtlas. Differential expression of the genes was analysed by t-test and survival analysis was performed according to gene expression.
High Expression of Complement Component 5 (C5) at Tumor Site Associates with Superior Survival in Ewing's Sarcoma Family of Tumour Patients.
Sex, Age, Specimen part, Disease
View SamplesPurpose: Unlike in most adult-onset cancers, an association between typical paediatric neoplasms and inflammatory triggers is rare. We studied whether immune system related genes are activated and have prognostic significance in Ewing sarcoma family of tumours (ESFT). Experimental design: Data-analysis was performed on gene expression profiles of 44 ESFT patient, 11 ESFT cell line, and 18 normal muscle tissue samples. 238 inflammation related genes were selected based on literature and a macrophage gene expression signature was derived from SymAtlas. Differential expression of the genes was analysed by t-test and survival analysis was performed according to gene expression.
High Expression of Complement Component 5 (C5) at Tumor Site Associates with Superior Survival in Ewing's Sarcoma Family of Tumour Patients.
Sex, Age, Specimen part, Disease, Cell line
View SamplesThe study demontrates differences in the transcriptome ( both of protein coding transcripts and long non-coding RNAs) in the unilateral ureteric obstruction model of renal fibrosis. Overall design: Renal tissue was studied from animals undergoing sham operation (as controls) or right ureteric ligation. Animals were sacrificed 2 and 8 days following ligation and the right kidney tissue was examined.
Whole-transcriptome analysis of UUO mouse model of renal fibrosis reveals new molecular players in kidney diseases.
Sex, Age, Specimen part, Cell line, Subject
View SamplesThe transcriptional activating and repressive functions performed by Trithorax and Polycomb group complexes, respectively, are critical for to maintain cellular fates in ontogeny and in cancer. Here we report that leukemias initiated by a Trithorax-related oncogene, MLL-AF9, depend upon the Polycomb Repressive Complex 2 (PRC2) to sustain a transformed cellular state. RNAi mediated suppression of PRC2 subunits is sufficient to inhibit proliferation of MLL-AF9 leukemias, with little impact on growth of non-transformed cells. This requirement is partly due to PRC2-mediated transcriptional repression of several anti-self-renewal regulators, including Cdkn2a. These results suggest that, unlike the classical antagonism generally observed between Polycomb and Trithorax group proteins during development, the activities of these two pathways can cooperate to promote myeloid neoplasia.
The Polycomb complex PRC2 supports aberrant self-renewal in a mouse model of MLL-AF9;Nras(G12D) acute myeloid leukemia.
No sample metadata fields
View Samples