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GSE35258
Arabidopsis thaliana
12 Downloadable Samples
Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The Clade A PP2C Highly ABA-Induced1 (HAI1, At5g59220) is strongly up-regulated by low water potential in an ABA-dependent manner. Using knockout mutants of hai1, we found that HAI1 functions as a negative regulator of low water potential-induced proline and osmoregulatory solute accumulation. We also found a relatively weak and limited interaction of HAI1 with the RCAR/PYL family of ABA receptors. This, plus its induced expression, suggest that HAI1 remains active during stress and attenuates specific aspects of drought response.
Publication Title
Unique drought resistance functions of the highly ABA-induced clade A protein phosphatase 2Cs.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Two Clade E Growth Regulating PP2Cs EGR1 and EGR2 (EGR1, At3g05640; EGR2, At5g27930) are strongly up regulated by low water but much less affected by ABA. EGR mutants maintained higher seedling root elongation and dry weight at low water potential and higher levels of stress protective metabolite proline.
Publication Title
Protein Phosphatase 2Cs and <i>Microtubule-Associated Stress Protein 1</i> Control Microtubule Stability, Plant Growth, and Drought Response.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
Ion Torrent Proton
Description
G protein coupled receptor (GPCR) signalling covers three major mechanisms. GPCR agonist engagement allows for the G proteins to bind to the receptor leading to a classical downstream signalling cascade. The second mechanism is via the utilization of the ß-arrestin signalling molecule and thirdly via transactivation dependent signalling. GPCRs can transactivate protein tyrosine kinase receptors (PTKR) to activate respective downstream signalling intermediates. In the past decade GPCR transactivation dependent signalling was expanded to show transactivation of serine/threonine kinase receptors (S/TKR). Kinase receptor transactivation enormously broadens the GPCR signalling paradigm. This work utilizes next generation RNA-sequencing to study the contribution of transactivation dependent signalling to total protease activated receptor (PAR)-1 signalling. Transactivation, assessed as gene expression, accounted for 50 percent of the total genes regulated by thrombin acting through PAR-1 in human coronary artery smooth muscle cells. GPCR transactivation of PTKRs is approximately equally important as the transactivation of the S/TKR with 209 and 177 genes regulated respectively, via either signalling pathway. This work shows that genome wide studies can provide powerful insights into GPCR mediated signalling pathways Overall design: Human CASMCS cells were subject to various treatments: basal, thrombin, thrombin + SB, thrombin + AG and thrombin + SB + AG. Gene expression was studies after 30 minutes to assess genes that are differentially expressed by treat emnt with agonists and antagonists. The agonoists and antagonists are associated with transactivation of GPCRs and the gene expression results will help identify relevant genes.
Publication Title
RNA sequencing to determine the contribution of kinase receptor transactivation to G protein coupled receptor signalling in vascular smooth muscle cells.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Histone deacetylase 3 (HDAC3) is the catalytic component of NCoR/SMRT corepressor complexes that mediate the actions of transcription factors implicated in the regulation of B cell development and function. We crossed Hdac3 conditional knockout mice with Mb1-Cre knockin animals to delete Hdac3 in early progenitor B cells. The spleens of Hdac3F/-Mb1-Cre+/- mice were virtually devoid of mature B cells, and B220+CD43+ B cell progenitors accumulated within the bone marrow. Quantitative deep sequencing of the immunoglobulin heavy chain locus from B220+CD43+ populations identified a defect in VHDJH recombination with a severe reduction in productive rearrangements, which directly corresponded to the loss of pre-B cells from Hdac3D/- bone marrow. For Hdac3D/- B cells that did show productive VDJ rearrangement, there was significant skewing toward the incorporation of proximal VH gene segments and a corresponding reduction in distal VH gene segment usage. While transcriptional effects within these loci were modest, Hdac3D/- progenitor cells displayed global changes in chromatin structure that likely hindered effective distal V-DJ recombination. Re-introduction of wild type Hdac3 restored normal B cell development, whereas an Hdac3 point mutant lacking deacetylase activity failed to complement this defect. Thus, the deacetylase activity of Hdac3 is required for the generation of mature B cells. Overall design: Bone marrow was isolated from Hdac3+/+Mb1cre+/- or Hdac3F/-Mb1cre+/- mice at 8 weeks of age. B220+CD43+ B cells were isolated from marrow by FACS and cells from two mice were pooled per sample. Total RNA isolated by Trizol extraction.
Publication Title
Deacetylase activity of histone deacetylase 3 is required for productive <i>VDJ</i> recombination and B-cell development.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Saccharomyces cerevisiae
- 15 Downloadable Samples
- Illumina HiSeq 2000
Description
Histone H3K4 methylation is connected to gene transcription from yeast to humans, but its mechanistic role in transcription and chromatin dynamics remains poorly understood. Here, we investigated the functions for Set1 and Jhd2, the sole H3K4 methyltransferase and H3K4 demethylase, respectively, in S. cerevisiae. Our data show that Set1 and Jhd2 predominantly co-regulate transcription. To further understand the role for H3K4 methylation, we overexpressed Flag epitope-tagged SET1-G990E (a dominant hyperactive allele of SET1) in yeast using the constitutive ADH1 promoter (ADH1p). As a control, we also overexpressed Flag epitope-tagged wild type SET1 in yeast. Analysis of gene expression in set1-null, jhd2-null and wild type SET1 or hypeactive SET1-G990E overexpressing mutants together revealed that the transcriptional regulation at a sub-set of genes, inclduing those governing glycogen metabolism and ribosome biogenesis, is highly sensitive to any change (i.e., loss or gain) in H3K4 methylation levels. Overall, we find combined activities of Set1 and Jhd2 via dynamic modulation of H3K4 methylation contribute to positive or negative transcriptional regulation at shared target genes. Overall design: Gene expression changes were generated from five different yeast strains representing wild type control, set1 null and jhd2 null mutants, and wild type SET1 or dominant hyperacive SET1-G990E overexpressing mutants. Three independent biological samples were grown for each strain, total RNA was isolated, libraries were prepared, sequenced, and analyzed separately.
Publication Title
Counteracting H3K4 methylation modulators Set1 and Jhd2 co-regulate chromatin dynamics and gene transcription.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 20 Downloadable Samples
- Illumina HiSeq 2500
Description
Squamous cell carcinoma (SCC) of lung is a devastating malignancy with no effective treatments, due to its complex genomic profile. Therefore, pre-clinical models mimicking its salient features are urgently needed. Here we describe mouse models bearing various combinations of genetic lesions predominantly found in human SCC. We show that Sox2 but not Fgfr1 overexpression in tracheobronchial basal cells combined with Cdkn2ab and Pten loss results in SCC closely resembling the human counterpart. Interestingly, Sox2;Pten;Cdkn2ab mice develop SCC with a more peripheral location when Club or Alveolar type 2 (AT2) cells are targeted. Our model highlights the essential role of Sox2 in promoting a squamous cell fate from different cells-of-origin and represents an invaluable tool for the developing better intervention strategies. Overall design: After RNA extraction and Bioanalyzer analysis, we processed samples with high quality RNA profiles using Illumina Hiseq2500.
Publication Title
SOX2 Is the Determining Oncogenic Switch in Promoting Lung Squamous Cell Carcinoma from Different Cells of Origin.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Background: To define changes in gene expression from stem cells and early progenitor cells lacking histone deacetylase 3 (Hdac3), we purified bone marrow Lineage Negative, Sca1/cKit positive and Flt3 negative cells from wild type and Vav-Cre/Hdac3Flox/- mice. These lineage-specific knock out mice lack Hdac3 throughout the hematopoietic system. To ensure that only cells lacking Hdac3 were measured, we used a Lox-STOP-Lox-ROSA26-GFP transgene such that any cell containing active Cre also expresses GFP.
Publication Title
HDAC3 is essential for DNA replication in hematopoietic progenitor cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Deletion of Hdac3 impaired DNA repair and greatly reduced chromatin compaction and heterochromatin content. Liver-specific deletion of Hdac3 culminated in hepatocellular carcinoma. The loss of genomic stability and the impaired response to DNA damage suggested that a high mutation rate stimulated the development of HCC. To begin to assess what pathways were involved in the formation of HCC, we performed gene expression analysis using cDNA microarrys.
Publication Title
Hdac3 is essential for the maintenance of chromatin structure and genome stability.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Small Cell Lung Cancer (SCLC) is the most aggressive type of lung cancer with early metastatic dissemination and invariable development of resistant disease for which no effective treatment is available to date. Mouse models of SCLC based on inactivation of Rb1 and Trp53 developed earlier showed frequent amplifications of two transcription factor genes: Nfib and Mycl. Overexpression of Nfib but not Mycl in SCLC mouse results in an enhanced and altered metastatic profile, and appears to be associated with genomic instability. NFIB promotes tumor heterogeneity with the concomitant expansive growth of poorly differentiated, highly proliferative, and invasive tumor cell populations. Consistent with the mouse data, NFIB expression in high-grade human neuroendocrine carcinomas correlates with advanced stage III/IV disease warranting its further assessment as a potentially valuable progression marker in a clinical setting. Overall design: Genomic DNA from mouse small cell lung tumor samples was analyzed by mate pair sequencing and low coverage sequencing. And RNA from Nfib overexpressing mouse small cell lung cancer cell lines was further analyzed for high quality RNA profiles using Illumina Hiseq2500. This series contains only RNA-seq data.
Publication Title
Transcription Factor NFIB Is a Driver of Small Cell Lung Cancer Progression in Mice and Marks Metastatic Disease in Patients.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- NextSeq 500
Description
Because injured mitochondria can accelerate cell death through the elaboration of oxidative free radicals and other mediators, it is somewhat paradoxical that proliferator gamma coactivator 1-alpha (PGC1a), a stimulator of increased mitochondrial abundance, protects stressed renal cells instead of potentiating injury. Here we report that PGC1a's induction of lysosomes via transcription factor EB (TFEB) may be pivotal for kidney protection. CRISPR and stable gene transfer showed that PGC1a knockout tubular cells were sensitized to the genotoxic stressor cisplatin whereas transgenic cells were protected. The biosensor mtKeima unexpectedly revealed that cisplatin blunts mitophagy both in cells and mice. PGC1a not only counteracted this effect but also raised basal mitophagy, as did the downstream mediator nicotinamide adenine dinucleotide (NAD+). PGC1a did not consistent affect known autophagy pathways modulated by cisplatin. Instead RNA sequencing identified coordinated regulation of lysosomal biogenesis via TFEB. This effector pathway was sufficiently important that inhibition of TFEB or lysosomes unveiled a striking harmful effect of excess PGC1a in cells and conditional mice. These results uncover an unexpected effect of cisplatin on mitophagy and PGC1a's exquisite reliance on lysosomes for kidney protection. Finally, the data illuminate TFEB as a novel target for renal tubular stress resistance. Overall design: 12 samples in total = 3 replicates each from 4 groups
Publication Title
TFEB-driven lysosomal biogenesis is pivotal for PGC1α-dependent renal stress resistance.
Sample Metadata Fields
Cell line, Subject
View Samples