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GSE107392
Mus musculus
11 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
T-cell prolymphocytic leukemia (T-PLL) is a rare and poor-prognostic mature T-cell malignancy. To address its incomplete molecular concept, we integrated large-scale profiling data of alterations in gene expression, allelic copy number (CN), and nucleotide sequences in 111 well-characterized patients. Besides prominent signatures of T-cell activation and prevalent clonal variants, we also identified novel hot-spots for CN variability, fusion molecules, alternative transcripts, and progression-associated dynamics. The overall lesional spectrum of T-PLL is mainly annotated to axes of DNA damage responses, T-cell receptor / cytokine signaling, and histone modulation. We formulate a multi-dimensional model of T-PLL pathogenesis centered around a unique combination of TCL1 overexpression with damaging ATM aberrations as initiating core lesions. The effects imposed by TCL1 cooperate with compromised ATM towards a leukemogenic phenotype of impaired DNA damage processing. Dysfunctional ATM appears inefficient in alleviating elevated redox burdens and telomere attrition and in evoking a p53-dependent apoptotic response to genotoxic insults. As non-genotoxic strategies, synergistic combinations of p53 reactivators and deacetylase inhibitors reinstate such cell death execution.
Publication Title
Actionable perturbations of damage responses by TCL1/ATM and epigenetic lesions form the basis of T-PLL.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Importantly increasing evidence shows that Hox genes such as Hoxa9 are key regulators of stem cell self-renewal and hematopoiesis. Hoxa9 is expressed in early hematopoietic progenitor cells and promotes stem cell expansion. In contrast Hoxa9 down regulation is associated with hematopoietic differentiation. In addition to its role in development, HOXA9 has been intensively studied because of its central role in human acute leukemias. Despite their obvious biomedical importance, the mechanisms through which Hoxa9 and its partner proteins exert their downstream functions are poorly understood.
Publication Title
The PAF complex synergizes with MLL fusion proteins at HOX loci to promote leukemogenesis.
Sample Metadata Fields
Sex, Specimen part, Cell line, Time
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina HiSeq 2000
Description
The most recurrently mutated oncogene in T-cell acute lymphoblastic leukemia (T-ALL) is NOTCH1. The core Notch complex consists of an ICN protein, a Maml cofactor, and the DNA binding factor Rbpj. The known direct cofactors of Notch appear to act nonselectively, homogeneously driving Notch gene expression functions. It is unclear whether there are direct cofactors of Notch that act selectively and heterogeneously regulate ICN. We discovered that Zmiz1, a Protein Inhibitor of Activated STAT (PIAS)-like coactivator, directly bound ICN1. ChIP-Seq showed that Zmiz1 selectively co-bound only a subset of Notch-regulated enhancers. This led to hypothesize that Zmiz1 regulates only a subset of Notch1 target genes. To investigate this, we performed RNA-Seq on four 8946 cell linesin which L1601P (activated Notch1) or Zmiz1 were expressed alone or in combination. Zmiz1 induced ~10% of Notch target genes. The Notch target gene that was most strongly induced by Zmiz1 was Myc. Our data suggest that Zmiz1 selectively amplifies a subset of Notch target genes with strong amplification of Myc. Overall design: RNA-Seq in a murine T-ALL cell line
Publication Title
The PIAS-like Coactivator Zmiz1 Is a Direct and Selective Cofactor of Notch1 in T Cell Development and Leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 5 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Composts are the products obtained after the aerobic degradation of different types of organic matter wastes and can be used as substrates or substrate/soil amendments. There are a small but increasing number of reports that suggest that foliar diseases may be reduced when using compost as growing medium compared to standard substrates. The purpose of this study was to unravel the gene expression alteration produced by the compost to gain knowledge about the mechanisms involved in the compost-induced systemic resistance.
Publication Title
Enhanced Botrytis cinerea resistance of Arabidopsis plants grown in compost may be explained by increased expression of defense-related genes, as revealed by microarray analysis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Lamin A/C was ablated in pancreatic acinar cells using Elastase1 driven, Cre-ErT mediated, LoxP recombination, causing excision of exons 10 and 11 of the Lmna gene
Publication Title
Lamin A/C Maintains Exocrine Pancreas Homeostasis by Regulating Stability of RB and Activity of E2F.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Interleukin 9 (IL-9) producing helper T (Th9) cells play a crucial role in allergic inflammation, autoimmunity, immunity to extracellular pathogens and anti-tumor immune response. In addition to Th9, Th2, Th17 and Foxp3+ Treg cells produce IL-9. Transcription factor that is critical for IL-9 induction in Th2, Th9 and Th17 cells has not been identified. Here we show that Foxo1, a forkhead family transcription factor, requires for IL-9 induction in Th9 and Th17 cells. We further show that inhibition of AKT enhances IL-9 induction in Th9 cells while it reciprocally regulates IL-9 and IL-17 in Th17 cells via Foxo1. Mechanistically, Foxo1 binds and transactivates IL-9 and IRF4 promoters in Th9, Th17 and iTregs. Furthermore, loss of Foxo1 attenuates IL-9 in mouse and human Th9 and Th17 cells, and ameliorates allergic inflammation in asthma. Our findings thus identify that Foxo1 is essential for IL-9 induction in Th9 and Th17 cells. Overall design: Transcriptional analysis of Th0 and TGF-beta 1 + IL-4 induced Th9 cells
Publication Title
Transcription factor Foxo1 is essential for IL-9 induction in T helper cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Drosophila melanogaster
- 18 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
In most embryos, the mid-blastula transition is a complex process featuring maternal RNA degradation, cell cycle pause, zygotic transcriptional activation and morphological changes. The nucleocytoplasmic (N/C) ratio has been proposed to control the multiple events at MBT. To understand the global transcriptional response to the changes of the N/C ratio, we profiled wild type and haploid embryos using cDNA microarrays at three developmental stages.
Publication Title
Coupling of zygotic transcription to mitotic control at the Drosophila mid-blastula transition.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Chronic low dose inorganic arsenic (iAs) exposure leads to changes in gene expression and epithelial-to-mesenchymal transformation. During this transformation, cells adopt a fibroblast-like phenotype accompanied by profound gene expression changes. While many mechanisms have been implicated in this transformation, studies that focus on the role of epigenetic alterations in this process are just emerging. DNA methylation controls gene expression in physiologic and pathologic states. Several studies show alterations in DNA methylation patterns in iAs-mediated pathogenesis, but these studies focused on single genes. We present a comprehensive genome-wide DNA methylation analysis using methyl-sequencing to measure changes between normal and iAs-transformed cells. Additionally, these differential methylation changes correlated positively with changes in gene expression and alternative splicing. Interestingly, most of these differentially methylated genes function in cell adhesion and communication pathways. To gain insight into how genomic DNA methylation patterns are regulated iAs-mediated carcinogenesis, we show that iAs probably targets CTCF binding at the promoter of DNA methyltransferases, regulating their expression. These findings reveal how transcription factor binding regulates DNA methyltransferase to reprogram the methylome in response to an environmental toxin.
Publication Title
Genome-wide DNA methylation reprogramming in response to inorganic arsenic links inhibition of CTCF binding, DNMT expression and cellular transformation.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Saccharomyces cerevisiae
- 8 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
In Saccharomyces cerevisiae, the maturation of both pre-rRNA and pre-small nucleolar RNAs (pre-snoRNAs) involves common factors, thereby providing a potential mechanism for the coregulation of snoRNA and rRNA synthesis. In this study, we examined the global impact of the double-stranded-RNA-specific RNase Rnt1p, which is required for pre-rRNA processing, on the maturation of all known snoRNAs. In silico searches for Rnt1p cleavage signals, and genome-wide analysis of the Rnt1p-dependent expression profile, identified seven new Rnt1p substrates. Interestingly, two of the newly identified Rnt1p-dependent snoRNAs, snR39 and snR59, are located in the introns of the ribosomal protein genes RPL7A and RPL7B. In vitro and in vivo experiments indicated that snR39 is normally processed from the lariat of RPL7A, suggesting that the expressions of RPL7A and snR39 are linked. In contrast, snR59 is produced by a direct cleavage of the RPL7B pre-mRNA, indicating that a single pre-mRNA transcript cannot be spliced to produce a mature RPL7B mRNA and processed by Rnt1p to produce a mature snR59 simultaneously. The results presented here reveal a new role of yeast RNase III in the processing of intron-encoded snoRNAs that permits independent regulation of the host mRNA and its associated snoRNA.
Publication Title
Genome-wide prediction and analysis of yeast RNase III-dependent snoRNA processing signals.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Post-transcriptional gene regulation by miRNAs and RNA binding proteins (RBP) is important in development, physiology and disease. To examine the interplay between miRNAs and the RBP ELAVL1 (a.k.a. HuR), we mapped miRNA binding sites on a transcriptome-wide scale in WT and Elavl1 knockout murine bone marrow-derived macrophages. Proximity of ELAVL1 binding sites attenuated miRNA binding to transcripts and promoted gene expression. Transcripts that regulate angiogenesis and macrophage/ endothelial cross talk were preferentially targeted by miRNAs, suggesting that ELAVL1 promotes angiogenesis, at least in part, by antagonism of miRNA function. We found that ELAVL1 antagonized binding of miR-27 to the 3'UTR of Zfp36 mRNA and alleviated miR-27-mediated suppression of the RBP ZFP36 (a.k.a. Tristetraprolin). Thus the miR-27-regulated mechanism synchronizes the expression of ELAVL1 and ZFP36. This study provides a resource for systems-level interrogation of post-transcriptional gene regulation in macrophages, a key cell type in inflammation, angiogenesis and tissue homeostasis. Overall design: Bone marrow derived macrpohges mRNA profiles of 7-day cultured wild type (WT) and Elavl1l-/- mouse bone marrow cells were generated by deep sequencing, with 4 biologic duplication, using Illumina GAII.
Publication Title
ELAVL1 modulates transcriptome-wide miRNA binding in murine macrophages.
Sample Metadata Fields
No sample metadata fields
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