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SRP050446
Mus musculus
12 Downloadable Samples
Description
The inflammatory response depends upon selective, rapid transcription initiation and high-level generation of gene products for defense against pathogens and environmental insult1,2. Kinase cascades are broadly employed for rapid transmission of extracellular information, thereby regulating the cell’s environmental response. These pathways play a prominent role in the inflammatory process. Several kinases directly phosphorylate histone proteins in chromatin, representing a mechanism for the rapid modification of chromatin with the potential to regulate selective transcription responses to environmental cues3-10. However, the molecular functions of specific histone phosphorylation events in transcription are poorly understood. Here, we demonstrate a direct effect of histone H3 phosphorylation at serine 28 (H3S28p) on transcription activation and describe a prominent role for H3S28p in the amplification of inflammatory gene transcription following stimulation of mouse macrophages with bacterial lipopolysaccharide (LPS). We identify MSK kinases as the non-redundant kinases that mediate the rapid, stimulation-dependent deposition of H3S28p on chromatin. Pharmacological approaches, including the use of a novel chemical agent, reveal that MSK inhibition abolishes stimulation-dependent accumulation of H3S28p at LPS-induced genes and reduces production of inflammatory gene products. Mechanistically, H3S28p directly increases transcriptional output by augmenting recruitment of the transcription co-activator and histone acetyltransferase (HAT) p300, and increasing its HAT activity. Our results reveal a delegated role for H3S28p in selective augmentation of transcription during the rapid cellular response to environmental cues. Overall design: Primary mouse bone marrow derived macrophages (BMDM) were used for NGS experiments. Briefly, BMDM were used unstimulated or following stimulation with S. typhosa LPS (100ng/mL) for the indicated period of time. Included in this submission are RNA-seq data for control DMSO treated BMDM (60'' and 120'' LPS stimulation), RMM-64 (5 uM) treated (60’ and 120’), SB747651A (5 uM) treated (60’ and 120’), and C646 (37.5 uM) teated (60’ and 120’). Further, ChIP-seq data for H3S28p time-course in BMDM stimulated with LPS includes one file each for 0’, 30’, 60’, 120’, 180’, 240’, and one file each at 0’ and 30’ for control DMSO treated, RMM-64 treated, SB747651A treated, and C646 treated BMDM. Also provided is an H3K27ac ChIP-seq time course in LPS stimulated BMDM: 0’, 30’, 120’, 180’, 240’.
Publication Title
Chromatin Kinases Act on Transcription Factors and Histone Tails in Regulation of Inducible Transcription.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 89 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Strain differences in gene expression in the hypothalamus of BXD recombinant inbred mice
Publication Title
Sex-specific modulation of gene expression networks in murine hypothalamus.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Danio rerio
- 35 Downloadable Samples
- IlluminaHiSeq1500
Description
This dataset describe the transcriptomic profiling of adult brain, gonades (testis and ovaries) of adult zebrafish exposed to 20µg/L of depleted uranium for 10 days. The progeny of the exposed fishes were also analysed at two-cells stage and 96 hours post fertilization Overall design: Biological samples (adult dissected tissues and whole embryos and larvae) were tested by RNASeq in duplicates
Publication Title
Whole transcriptome data of zebrafish exposed to chronic dose of depleted uranium.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 20 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Approximately 2.5 mg dry Col-0 seedlings were surface sterilized and stratified for 2 days at 4degreesC in liquid media containing 1.5% sucrose (w/v) before being transferred to light with constant shaking at 100 rpm on an orbital shaker. After 7 days, the seedling clusters were subjected to the treatments for 1 hr followed by total RNA isolation using the RNAqueous kit (Ambion). Each treatment was performed in triplicate or quadruplicate. All labeling (Enzo) and hybridization (Affymetrix) procedures were performed as directed by the manufacturers. Raw probe intensities output by the Affymetrix MAS software were processed using the RMA algorithm to obtain an expression measure for each gene on each array.
Publication Title
Identification of inhibitors of auxin transcriptional activation by means of chemical genetics in Arabidopsis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
DOT1L-mediated H3K79 methylation in chromatin is dispensable for Wnt pathway-specific and other intestinal epithelial functions.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Leukemia stem cells (LSCs) are an attractive target in treatment of many types of blood cancers. There remains an incomplete understanding of the epigenetic mechanisms driving LSC formation and maintenance, and how this compares to the epigenetic regulation of normal hematopoietic stem cells (HSCs).
Publication Title
Haploinsufficiency of Dnmt1 impairs leukemia stem cell function through derepression of bivalent chromatin domains.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
We used microarrays to detail the differentail gene expression between intestinal Lgr5(hi) stem cells and differentiated cells
Publication Title
DOT1L-mediated H3K79 methylation in chromatin is dispensable for Wnt pathway-specific and other intestinal epithelial functions.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Transplantation with low numbers of hematopoietic stem cells (HSCs), found in many of the publically accessible cryopreserved umbilical cord blood (UCB) units, leads to delayed time to engraftment, high graft failure rates, and early mortality in many patients. A chemical screen in zebrafish identified the prostaglandin compound, 16,16 dimethyl prostaglandin E2 (dmPGE2), to be a critical regulator of hematopoietic stem cell homeostasis. We hypothesized that an ex vivo modulation with dmPGE2 prior to transplantation would lead to enhanced engraftment by increasing the effective dose of hematopoietic stem cells (HSCs) in cord blood. A phase I trial of reduced-intensity double UCB transplantation was performed to evaluate safety, rates of engraftment and fractional chimerism of dmPGE2 enhanced UCB units. To explore potential causes of the lack of enhanced efficacy in the first cohort, we characterized HSCs to determine whether the prostaglandin pathway was being activated under the ex vivo incubation conditions (4C, 10M dmPGE2, 60 minutes). Incubation conditions were identified (37C, 10M dmPGE2, 120 minutes) that maximize the activation of the prostaglandin pathway by dmPGE2 in human CD34+ cells.
Publication Title
Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Umbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) for use in allogeneic transplantation. Key advantages of UCB are rapid availability and less stringent requirements for HLA matching. However, UCB contains an inherently limited HSC count, which is associated with delayed time to engraftment, high graft failure rates and early mortality. 16,16 dimethyl prostaglandin E2 (dmPGE2) was previously identified to be a critical regulator of HSC homeostasis and we hypothesized that a brief ex vivo modulation could improve patient outcomes by increasing the effective dose of HSCs.
Publication Title
Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Umbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) for use in allogeneic transplantation. Key advantages of UCB are rapid availability and less stringent requirements for HLA matching. However, UCB contains an inherently limited HSC count, which is associated with delayed time to engraftment, high graft failure rates and early mortality. 16,16 dimethyl prostaglandin E2 (dmPGE2) was previously identified to be a critical regulator of HSC homeostasis and we hypothesized that a brief ex vivo modulation could improve patient outcomes by increasing the "effective dose" of HSCs.
Publication Title
Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation.
Sample Metadata Fields
Specimen part, Treatment
View Samples