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SRP056313
Mus musculus
10 Downloadable Samples
Illumina HiSeq 2000
Description
Pre-B and pre-T lymphocytes must orchestrate a transition from a highly proliferative state to a quiescent one during development. Cyclin D3 is essential for these cells’ proliferation, but little is known about its post-translational regulation at this stage. Here, we show that the dual specificity tyrosine-regulated kinase 1A (DYRK1A) restrains Cyclin D3 protein levels by phosphorylating T283 to induce its degradation. Loss of DYRK1A activity, via genetic inactivation or pharmacologic inhibition, caused accumulation of Cyclin D3 protein, incomplete repression of E2F-mediated gene transcription, and failure to properly couple cell cycle exit with differentiation. Expression of a non-phosphorylatable Cyclin D3 T283A mutant recapitulated these defects, while inhibition of Cyclin D:CDK4/6 mitigated the effects of DYRK1A inhibition. These data uncover a previously unknown role for DYRK1A in lymphopoiesis, and demonstrate how Cyclin D3 protein stability is negatively regulated during exit from the proliferative phases of B and T cell development. Overall design: 5 cell populations were analyzed (small pre-B cells, large pre-B cells, quiescent CD4+CD8+ thymocytes, cycling CD4+CD+ thymocytes, and mature granulocytes) from 2 Control mice (pooled) and 2 DYRK1A-deficient mice (pooled) for a total of 10 samples.
Publication Title
DYRK1A controls the transition from proliferation to quiescence during lymphoid development by destabilizing Cyclin D3.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
Conditional knockout of Snai1 in the mouse intestinal epithlium results in apoptotic loss of crypt base columnar cells and bias towards differentiation of secretory lineages. In vitro organoid cultures derived from Snail conditional knockout mice also undergo apoptosis when Snai1 is deleted.
Publication Title
Snai1 regulates cell lineage allocation and stem cell maintenance in the mouse intestinal epithelium.
Sample Metadata Fields
No sample metadata fields
View Samples- Zea mays
- 15 Downloadable Samples
- Illumina HiSeq 1500
Description
UV-B radiation affects leaf growth in a wide range of species. In this work, we demonstrate that UV-B levels present in solar radiation inhibits maize leaf growth without causing any other visible stress symptoms, including accumulation of DNA damage. We conducted kinematic analyses of cell division and expansion to understand the impact of UV-B radiation on these cellular processes. Our results demonstrate that the decrease in leaf growth is a consequence of a reduction in cell production, and a shortened growth zone (GZ) in UV-B irradiated leaves. To determine the molecular pathways involved in UV-B inhibition of leaf growth, we performed RNA sequencing on isolated GZ tissues of control and UV-B exposed plants. Our results show a link between the observed leaf growth inhibition and the expression of specific cell cycle and developmental genes, including Growth Regulating Factors (GRFs) and transcripts for proteins participating in different hormone pathways. Overall design: Factorial design with two factors: Treatment (control vs UV-B) x Zone I (0-1cm from base of the leaf), 2 (1-2cm from base of the leaf) and 3 (2-3cm from base of the leaf), 3 replicates
Publication Title
UV-B Inhibits Leaf Growth through Changes in Growth Regulating Factors and Gibberellin Levels.
Sample Metadata Fields
Specimen part, Subject
View Samples- Zea mays
- 8 Downloadable Samples
- Illumina Genome Analyzer II
Description
P1 encodes an R2R3-MYB transcription factor responsible for the accumulation of insecticidal flavones in maize silks and red phlobaphene pigments in pericarps and other floral tissues, which contributed to making P1 an important visual marker since the dawn of modern genetics. We conducted RNA-Seq using pericarps at two different stages, 14 and 25 days after pollination (DAP). High-throughput sequencing using the Illumina platform resulted in the generation of ~20 million high quality reads, from which ~90% aligned to the recently completed maize genome sequence corresponding to ~5 million reads for each one of the four samples. Overall design: Examination of two different RNA samples from two different stages of maize pericarp tissues.
Publication Title
A genome-wide regulatory framework identifies maize pericarp color1 controlled genes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Zea mays
- 2 Downloadable Samples
- Illumina Genome Analyzer II
Description
P1 encodes an R2R3-MYB transcription factor responsible for the accumulation of insecticidal flavones in maize silks and red phlobaphene pigments in pericarps and other floral tissues, which contributed to making P1 an important visual marker since the dawn of modern genetics. We conducted RNA-Seq using from maize silks obtained at 2-3 days after emergence. High-throughput sequencing using the Illumina platform resulted in the generation of ~14 million high quality reads, corresponding to ~7 million reads for each sample, from which 76% aligned to the maize genome. Overall design: Examination of two different RNA samples from maize silks obtained at 2-3 days after emergence
Publication Title
A genome-wide regulatory framework identifies maize pericarp color1 controlled genes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Osmotic stress induces phosphorylation of histone H3 at threonine 3 in pericentromeric regions of Arabidopsis thaliana.
Sample Metadata Fields
Age, Specimen part
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Histone phosphorylation plays key roles in stress-induced transcriptional reprogramming in metazoans but its function(s) in land plants has remained relatively unexplored. Here we report that an Arabidopsis mutant defective in At3g03940 and At5g18190, encoding closely related Ser/Thr protein kinases, shows pleiotropic phenotypes including dwarfism and hypersensitivity to osmotic/salt stress. The double mutant has reduced global levels of phosphorylated histone H3 threonine 3 (H3T3ph), which are not enhanced, unlike the response in the wild type, by drought-like treatments. Genome-wide analyses revealed increased H3T3ph, slight enhancement in trimethylated histone H3 lysine 4 (H3K4me3), and a modest decrease in histone H3 occupancy in pericentromeric/knob regions of wild type plants under osmotic stress. However, despite these changes in heterochromatin, transposons and repeats remained largely transcriptionally repressed. In contrast, this reorganization of heterochromatin was mostly absent in the double mutant, which even under normal conditions exhibited lower H3T3ph levels in pericentromeric regions, and a few transposons and repeat sequences showed modest transcriptional activation. Interestingly, within actively transcribed protein-coding genes, H3T3ph density was minimal in 5 genic regions, coincidental with a peak of H3K4me3 accumulation. This pattern was not affected in the double mutant, implying the existence of additional H3T3 protein kinases in Arabidopsis. Our results suggest that At3g03940 and At5g18190 are involved in the phosphorylation of H3T3 in pericentromeric/knob regions and that this repressive epigenetic mark may be important for maintaining proper heterochromatic organization and, possibly, chromosome function(s).
Publication Title
Osmotic stress induces phosphorylation of histone H3 at threonine 3 in pericentromeric regions of Arabidopsis thaliana.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Murine pancreatic beta cell line MIN6 was growth at two different concentrations of glucose (22,2 and 5,5 mM of glucose), 37C, 5% CO2 and was treated at four different concentrations of human amylin (0, 1, 10 and 20 uM) during three different times (2, 12 and 24 hours)
Publication Title
Impairment of the ubiquitin-proteasome pathway is a downstream endoplasmic reticulum stress response induced by extracellular human islet amyloid polypeptide and contributes to pancreatic beta-cell apoptosis.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Impaired DNA replication is a hallmark of cancer and a cause of genomic instability. We report that, in addition to causing genetic change, impaired DNA replication during embryonic development can have major epigenetic consequences for a genome. In a genome-wide screen, we identified impaired DNA replication as causing increased expression from a repressed transgene in Caenorhabditis elegans. The acquired expression state behaved as an “epiallele,” being inherited for multiple generations before fully resetting. Derepression was not restricted to the transgene but was caused by a global reduction in heterochromatin-associated histone modifications due to the impaired retention of modified histones on DNA during replication in the early embryo. Impaired DNA replication during development can therefore globally derepress chromatin, creating new intergenerationally inherited epigenetic expression states. Overall design: 3 replicates of div-1 mutant worms and N2 wild type worms
Publication Title
Impaired DNA replication derepresses chromatin and generates a transgenerationally inherited epigenetic memory.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The statins are a family of inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase enzyme, which converts acetyl-CoA into mevalonic acid. Since HMG-CoA reductase catalyzes the rate-limiting step in the mevalonate pathway of cholesterol biosynthesis, it was thought that the major clinical benefit of statins was to reduce cholesterol levels in the bloodstream; statins are thus in wide clinical use for the prevention and treatment of cardiovascular disease. Nonetheless, mevalonate is also the precursor of isoprenoid compounds, which are substrates for the post-translational modification of many proteins involved in cell signaling. The blockade of isoprenoid synthesis might explain the pleiotropic effects described for statins in extrahepatic tissues, including inhibition of pathogen infection and anti-inflammatory and immunomodulatory activities.
Publication Title
A lovastatin-elicited genetic program inhibits M2 macrophage polarization and enhances T cell infiltration into spontaneous mouse mammary tumors.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples