SbrI and SbrR are an extracytoplasmic function sigma factor and its cognate anti-sigma factor, respectively. To identify the SbrIR regulon, we measured gene expression in wild type PAO1 , PAO1 sbrR, and PAO1 sbrIR mutants using microarrays.
σ Factor and Anti-σ Factor That Control Swarming Motility and Biofilm Formation in Pseudomonas aeruginosa.
No sample metadata fields
View SamplesTranscriptional crosstalk between mammary gland, liver and adipose tissue
Homeorhetic adaptation to lactation: comparative transcriptome analysis of mammary, liver, and adipose tissue during the transition from pregnancy to lactation in rats.
No sample metadata fields
View SamplesBCRABL1+ precursor B-cell acute lymphoblastic leukemia (BCR ABL1+ B-ALL) is an aggressive hematopoietic neoplasm characterized by a block in differentiation due in part to the somatic loss of transcription factors required for B-cell development. We hypothesized that overcoming this differentiation block by forcing cells to reprogram to the myeloid lineage would reduce the leukemogenicity of these cells. We found that primary human BCRABL1+ B-ALL cells could be induced to reprogram into macrophage-like cells by exposure to myeloid differentiation-promoting cytokines in vitro or by transient expression of the myeloid transcription factor C/EBP or PU.1. The resultant cells were clonally related to the primary leukemic blasts but resembled normal macrophages in appearance, immunophenotype, gene expression, and function. Most importantly, these macrophage-like cells were unable to establish disease in xenograft hosts, indicating that lineage reprogramming eliminates the leukemogenicity of BCRABL1+ B-ALL cells, and suggesting a previously unidentified therapeutic strategy for this disease. Finally, we determined that myeloid reprogramming may occur to some degree in human patients by identifying primary CD14+ monocytes/ macrophages in BCRABL1+ B-ALL patient samples that possess the BCRABL1+ translocation and clonally recombined VDJ regions.
Reprogramming of primary human Philadelphia chromosome-positive B cell acute lymphoblastic leukemia cells into nonleukemic macrophages.
No sample metadata fields
View SamplesTo compare the gene expression profiles of unpassaged, proliferating HUVEC and human iris, retinal and choroidal microvascular endothelial cells.
Comparative gene expression profiling of human umbilical vein endothelial cells and ocular vascular endothelial cells.
Specimen part
View SamplesOur overall objective is to identify key differences in gene expression signaling pathways in the epithelial and intralobular stromal compartments during prepartum mammary remodeling and development in the dry cow.
Transcriptome analysis of epithelial and stromal contributions to mammogenesis in three week prepartum cows.
No sample metadata fields
View SamplesPseudomonas aeruginosa is a virulent opportunistic pathogen responsible for high morbity in COPD, burns , implanted medical devices and cystic fibrosis.
Anr and its activation by PlcH activity in Pseudomonas aeruginosa host colonization and virulence.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Promiscuous targeting of bromodomains by bromosporine identifies BET proteins as master regulators of primary transcription response in leukemia.
Cell line, Treatment
View SamplesBromodomains (BRDs) have emerged as compelling targets for cancer therapy. The development of selective and potent BET inhibitors and their significant activity in diverse tumor models has rapidly translated into clinical studies and has motivated drug development efforts targeting non-BET BRDs. However, the complex multidomain/subunit architecture of bromodomain protein complexes complicates predictions of consequences of their pharmacological targeting. To address this issue we developed a promiscuous bromodomain inhibitor (bromosporine, BSP) that broadly targets BRDs (including BETs) with nanomolar affinity, creating a tool for the identification of cellular processes and diseases where BRDs have a regulatory function. As a proof of principle we studied the effect of BSP in leukemic cell-lines known to be sensitive to BET inhibition and found as expected strong anti-proliferative activity. Comparison of the modulation of transcriptional profiles by BSP at short inhibitor exposure resulted in a BET inhibitor signature but no significant additional changes in transcription that could account for inhibition of other BRDs. Thus, non-selective targeting of BRDs identified BETs, but not other BRDs, as master regulators of a context dependent primary transcription response.
Promiscuous targeting of bromodomains by bromosporine identifies BET proteins as master regulators of primary transcription response in leukemia.
Cell line, Treatment
View SamplesBromodomains (BRDs) have emerged as compelling targets for cancer therapy. The development of selective and potent BET inhibitors and their significant activity in diverse tumor models has rapidly translated into clinical studies and has motivated drug development efforts targeting non-BET BRDs. However, the complex multidomain/subunit architecture of bromodomain protein complexes complicates predictions of consequences of their pharmacological targeting. To address this issue we developed a promiscuous bromodomain inhibitor (bromosporine, BSP) that broadly targets BRDs (including BETs) with nanomolar affinity, creating a tool for the identification of cellular processes and diseases where BRDs have a regulatory function. As a proof of principle we studied the effect of BSP in leukemic cell-lines known to be sensitive to BET inhibition and found as expected strong anti-proliferative activity. Comparison of the modulation of transcriptional profiles by BSP at short inhibitor exposure resulted in a BET inhibitor signature but no significant additional changes in transcription that could account for inhibition of other BRDs. Thus, non-selective targeting of BRDs identified BETs, but not other BRDs, as master regulators of a context dependent primary transcription response.
Promiscuous targeting of bromodomains by bromosporine identifies BET proteins as master regulators of primary transcription response in leukemia.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Evolutionary routes and KRAS dosage define pancreatic cancer phenotypes.
No sample metadata fields
View Samples