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GSE71617
Homo sapiens
14 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Functionally distinct patterns of nucleosome remodeling at enhancers in glucocorticoid-treated acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Precise nucleosome positioning is an increasingly recognized feature of promoters and enhancers, reflecting complex contributions of DNA sequence, nucleosome positioning, histone modification and transcription factor binding to enhancer activity and regulation of gene expression. Changes in nucleosome position and occupancy, histone variants and modifications, and chromatin remodeling are also critical elements of dynamic transcriptional regulation, but poorly understood at enhancers. We investigated glucocorticoid receptor-associated (GR) nucleosome dynamics at enhancers in acute lymphoblastic leukemia. For the first time, we demonstrate functionally distinct modes of nucleosome remodeling upon chromatin binding by GR, which we term central, non-central, phased, and minimal. Central and non-central remodeling reflect nucleosome eviction by GR and cofactors, respectively. Phased remodeling involves nucleosome repositioning and is associated with rapidly activated enhancers and induction of gene expression. Minimal remodeling sites initially have low levels of enhancerassociated histone modification, but the majority of these regions gain H3K4me2 or H3K27Ac to become de novo enhancers. Minimal remodeling regions are associated with gene ontologies specific to decreased B cell number and mTOR inhibition and may make unique contributions to glucocorticoid-induced leukemia cell death. Our findings form a novel framework for understanding the dynamic interplay between transcription factor binding, nucleosome remodeling, enhancer function, and gene expression in the leukemia response to glucocorticoids.
Publication Title
Functionally distinct patterns of nucleosome remodeling at enhancers in glucocorticoid-treated acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
NextSeq 500
Description
Malignant rhabdoid tumors (MRT) are highly aggressive pediatric cancers that respond poorly to current therapies. We screened several MRT cell lines each with large-scale RNAi, CRISPR-Cas9, and small-molecule libraries to identify potential drug targets specific for these cancers. We discovered MDM2 and MDM4, the canonical negative regulators of p53, as significant vulnerabilities. Using two compounds currently in clinical development, idasanutlin and ATSP-7041, we show that MRT cells are more sensitive than other p53 wild-type cancer cell lines to MDM2 and dual MDM2/4 inhibition in vitro. These compounds cause significant upregulation of the p53 pathway in MRT cells, and sensitivity is ablated by CRISPR-Cas9-mediated inactivation of TP53. We show that loss of SMARCB1, a subunit of the SWI/SNF (BAF) complex mutated in nearly all MRT, sensitizes cells to MDM2 and MDM2/4 inhibition by enhancing p53-mediated apoptosis. Both MDM2 and MDM2/4 inhibition slowed MRT xenograft growth in vivo, with a five-day idasanutlin pulse causing marked regression of all xenografts including durable complete responses in 50% of mice. Together, these studies identify a genetic connection between mutations in the SWI/SNF chromatin-remodeling complex and the tumor suppressor gene p53, and provide preclinical evidence to support the targeting of MDM2 and MDM4 in this often-fatal pediatric cancer. Overall design: RNA-seq in TTC642 MRT cells treated with idasanutlin compared to DMSO
Publication Title
MDM2 and MDM4 Are Therapeutic Vulnerabilities in Malignant Rhabdoid Tumors.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 31 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Zinc is an essential micronutrient in pregnancy and zinc deficiency impairs fetal growth. We used a mouse model of moderate zinc deficiency to determine how zinc is important to placental morphogenesis.
Publication Title
Zinc is a critical regulator of placental morphogenesis and maternal hemodynamics during pregnancy in mice.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Immune system homeostasis depends on signals that drive effector (like secretion of pro-inflammatory cytokines like IFNg) and regulatory (like secretion of the anti-inflammatory cytokine IL-10) functions.
Publication Title
The cholesterol biosynthesis pathway regulates IL-10 expression in human Th1 cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
We have previously identified a significant increase in chloroplast reactive oxygen species in wounded leaves of Arabidopsis and other plants, which is light-dependent (Flor-Henry et al. (2004) BMC Plant Biology 4:19). The aims of this study were to (i) examine the early response to mechanical wounding in Arabidopsis leaves, (ii) test the hypothesis that light-dependent chloroplast ROS may play a role in signalling for changes in gene expression in wounded leaves, and (iii) examine the broader impact of the light environment on the wound response in Arabidopsis.
Publication Title
Light exerts multiple levels of influence on the Arabidopsis wound response.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 10 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Transcriptome analyses using a wild-type strain of Saccharomyces cerevisiae were performed to assess the overall pattern of gene expression during the transition from glucose-based fermentative to glycerol-based respiratory growth. These experiments revealed a complex suite of metabolic and structural changes associated with the adaptation process. Alterations in gene expression leading to remodeling of various membrane transport systems and the cortical actin cytoskeleton were observed. Transition to respiratory growth was accompanied by alterations in transcript patterns demonstrating not only a general stress response, as seen in earlier studies, but also the oxidative and osmotic stress responses. In some contrast to earlier studies, these experiments identified modulation of expression for many genes specifying transcription factors during the transition to glycerol-based growth. Importantly and unexpectedly, an ordered series of changes was seen in transcript levels from genes encoding components of the TFIID, SAGA (Spt-Ada-Gcn5-Acetyltransferase), and SLIK (Saga LIKe) complexes and all three RNA polymerases, suggesting a modulation of structure for the basal transcriptional machinery during adaptation to respiratory growth. In concert with data given in earlier studies, the results presented here highlight important aspects of metabolic and other adaptations to respiratory growth in yeast that are common to utilization of multiple carbon sources. Importantly, they also identify aspects specific to adaptation of this organism to growth on glycerol as sole carbon source.
Publication Title
Transcriptome profiling of Saccharomyces cerevisiae during a transition from fermentative to glycerol-based respiratory growth reveals extensive metabolic and structural remodeling.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 22 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Rsf1p is a putative transcription factor required for efficient growth using glycerol as sole carbon source but not for growth on the alternative respiratory carbon source ethanol.
Publication Title
Rsf1p is required for an efficient metabolic shift from fermentative to glycerol-based respiratory growth in S. cerevisiae.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 5 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
A putative yeast mitochondrial upstream activating sequence (UAS) was used in a one-hybrid screening procedure that identified the YJR127C ORF on chromosome X. This gene was previously designated ZMS1 and is listed as a transcription factor on the SGD website. Real time RT-PCR assays showed that expression of YJR127C/ZMS1 was glucose-repressible, and a deletion mutant for the gene showed a growth defect on glycerol-based but not on glucose- or ethanol-based medium. Real time RT-PCR analyses identified severely attenuated transcript levels from GUT1 and GUT2 to be the source of that growth defect, the products of GUT1 and GUT2 are required for glycerol utilization. mRNA levels from a large group of mitochondria- and respiration-related nuclear genes also were shown to be attenuated in the deletion mutant. Importantly, transcript levels from the mitochondrial OLI1 gene, which has an associated organellar UAS, were attenuated in the DeltaYJR127C mutant during glycerol-based growth, but those from COX3 (OXI2), which lacks an associated mitochondrial UAS, were not. Transcriptome analysis of the glycerol-grown deletion mutant showed that genes in several metabolic and other categories are affected by loss of this gene product, including protein transport, signal transduction, and others. Thus, the product of YJR127C/ZMS1 is involved in transcriptional control for genes in both cellular genetic compartments, many of which specify products required for glycerol-based growth, respiration, and other functions.
Publication Title
The YJR127C/ZMS1 gene product is involved in glycerol-based respiratory growth of the yeast Saccharomyces cerevisiae.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 73 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Erythropoiesis in mammals replenishes the circulating red blood cell (RBC) pool from hematopoietic stem/progenitor cells (HSPCs). Two distinct erythropoietic programs have been described. In the first trimester, hematopoietic precursors in the fetal yolk sac follow a primitive pattern of erythropoiesis. However, in the second trimester, hematopoietic stem cells (HSCs) from the fetal liver and later from the bone marrow differentiate by a definitive program of erythropoiesis to yield enucleated erythrocytes. RBCs can also be derived from human induced pluripotent stem cells (hiPSCs) and can express many of the red cell proteins required for normal erythrocyte function, presaging in vitro RBC production for clinical use. However, expansion and enucleation from hiPSCs is less efficient than with erythroblasts (EBs) derived from adult or cord blood progenitors. We hypothesized that substantial differential gene expression during erythroid development from hiPSCs compared to that from adult blood or cord blood precursors could account for these hitherto unexplained differences in proliferation and enucleation. We have therefore grown EBs from human adult and cord blood progenitors and from hiPSCs. Gene expression during erythroid culture from each erythroblast source was analyzed using algorithms designed to cluster co-expressed genes in an unsupervised manner and the function of differentially expressed genes explored by gene ontology. Using these methods we identify specific patterns of gene regulation for adult- and cord- derived EBs, regardless of the medium used, that are substantially distinct from those observed during the differentiation of EBs from hiPSC progenitors which largely follows a pattern of primitive erythropoiesis.
Publication Title
Distinct gene expression program dynamics during erythropoiesis from human induced pluripotent stem cells compared with adult and cord blood progenitors.
Sample Metadata Fields
Specimen part
View Samples