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GSE18198
Homo sapiens
6 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
NOTCH proteins regulate signaling pathways involved in cellular differentiation, proliferation and death. Overactive Notch signaling as been observed in numerous cancers and has been extensively studied in the context of T-cell acute lymphoblastic leukemia (T-ALL) where more than 50% of pateints harbour mutant NOTCH1. Small molecule modulators of these proteins would be important for understanding the role of NOTCH proteins in malignant and normal biological processes.
Publication Title
Direct inhibition of the NOTCH transcription factor complex.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 133 Downloadable Samples
NextSeq 500
Description
The mammalian genome contains thousands of loci that transcribe long noncoding RNAs (lncRNAs), some of which are known to play critical roles in diverse cellular processes through a variety of mechanisms. While some lncRNA loci encode RNAs that act non-locally (in trans), emerging evidence indicates that many lncRNA loci act locally (in cis) to regulate expression of nearby genes—for example, through functions of the lncRNA promoter, transcription, or transcript itself. Despite their potentially important roles, it remains challenging to identify functional lncRNA loci and distinguish among these and other mechanisms. To address these challenges, we developed a genome-scale CRISPR-Cas9 activation screen targeting more than 10,000 lncRNA transcriptional start sites (TSSs) to identify noncoding loci that influence a phenotype of interest. We found 11 novel lncRNA loci that, upon recruitment of an activator, each mediate BRAF inhibitor resistance in melanoma. Most candidate loci appear to regulate nearby genes. Detailed analysis of one candidate, termed EMICERI, revealed that its transcriptional activation results in dosage-dependent activation of four neighboring protein-coding genes, one of which confers the resistance phenotype. Our screening and characterization approach provides a CRISPR toolkit to systematically discover functions of noncoding loci and elucidate their diverse roles in gene regulation and cellular function. Overall design: RNA-seq on A375 cells overexpressing candidate lncRNA or protein-coding gene.
Publication Title
Genome-scale activation screen identifies a lncRNA locus regulating a gene neighbourhood.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 3 Downloadable Samples
Description
RNA-seq and ATAC-seq data to understand how gene regulation and chromatin accessibility correlates with function enrichment in CRISPR screen for melanoma drug resistance
Publication Title
Genome-scale activation screen identifies a lncRNA locus regulating a gene neighbourhood.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 21 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Abstract of publicaton: CD4/CD8 double-positive (DP) thymocytes express the transcriptional repressor Histone Deacetylase 7 (HDAC7), a class IIa HDAC that is exported from the cell nucleus after T cell receptor (TCR) engagement. Through signal-dependent nuclear export, class IIa HDACs such as HDAC7 mediate signal-dependent changes in gene expression that are important to developmental fate decisions in multiple tissues. We report that HDAC7 is exported from the cell nucleus during positive selection in thymocytes, and regulates genes mediating the coupling between TCR engagement and downstream events that determine cell survival. Thymocytes lacking HDAC7 are inefficiently positively selected due to a severely shortened lifespan and exhibit a truncated repertoire of TCR Jalpha segments. The expression of multiple important mediators and modulators of the response to TCR engagement is altered in HDAC7-deficient thymocytes, resulting in increased tonic MAP kinase activity that contributes to the observed loss of viability. Remarkably, the activity of Protein Kinase D, the kinase that mediates nuclear export of HDAC7 in response to TCR signaling, is also increased in HDAC7-deficient thymocytes, suggesting that HDAC7 nuclear export governs a self-sustaining auto-excitatory loop. These experiments add to the understanding of the life/death decision in thymic T cell development, define a novel function for class IIa HDACs, and point to a novel feed-forward mechanism whereby these molecules regulate their own state and mediate stable developmental transitions. Title of manuscript: Nuclear Export of Histone Deacetylase 7 During Thymic Selection Mediates Immune Self-tolerance. abstract of manuscript: Histone Deacetylase 7 (HDAC7) is a TCR signal-dependent regulator of differentiation that is highly expressed in CD4/CD8 double-positive (DP) thymocytes. Here we examine the effect of blocking TCR-dependent nuclear export of HDAC7 during thymic selection, through expression of a signal-resistant mutant of HDAC7 (HDAC7-?P) in thymocytes. We find that HDAC7-?P Transgenic thymocytes exhibit a profound block in negative thymic selection, but can still undergo positive selection, resulting in the escape of autoreactive T cells into the periphery. Gene expression profiling reveals a comprehensive suppression of the negative selection-associated gene expression program in DP thymocytes, associated with a defect in the activation of MAP kinase pathways by TCR signals. The consequence of this block in vivo is a lethal autoimmune syndrome involving the exocrine pancreas and other abdominal organs. These experiments establish a novel molecular model of autoimmunity and cast new light on the relationship between thymic selection and immune self-tolerance. Goal of Microarray experiment: We did these experiments to determine how alteration of the function of HDAC7, a site-specific and signal-dependent repressor of transcription, changes gene expression in CD4/CD8 DP thymocytes.
Publication Title
Histone deacetylase 7 regulates cell survival and TCR signaling in CD4/CD8 double-positive thymocytes.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 72 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The circadian clock orchestrates rhythms in physiology and behavior, allowing the organism to adapt to daily environmental changes. Recently, efforts have been made to unravel the connection between the circadian clock and metabolism and to understand how the peripheral clock in different organs coordinates circadian responses to maintain metabolic homeostasis. It is becoming clear that diet can influence diurnal rhythms, however, the molecular mechanisms responsible for alterations in daily oscillations and how tissue-specific clocks interpret a nutritional challenge are not well understood. Here, we reveal tissue-specific circadian plasticity in response to a ketogenic diet (KD) in both the liver and intestine and a remarkable deviation within these two tissues following subsequent carbohydrate supplementation. KD caused a dramatic change in the circadian transcriptome in both liver and intestine in a tissue-specific fashion. In particular, both the amplitude of clock genes as well as specific BMAL1 recruitment was profoundly altered by KD while the intestinal clock was devoid of such plasticity. While PPARG nuclear accumulation was circadian in both tissues, it showed substantial phase specificity as did downstream targets. Finally, the gut and liver clocks had distinct responses to carbohydrate supplementation to KD composition, suggesting a higher plasticity in the ileum whose gene expression was almost restored to control baseline. For the first time our results demonstrate how nutrients modulate clock function in a tissue-specific manner, suggesting that a food stress arouses unique circadian molecular signatures in distinct peripheral tissues.
Publication Title
Distinct Circadian Signatures in Liver and Gut Clocks Revealed by Ketogenic Diet.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Leanness is associated with increased lifespan and is linked to favorable metabolic conditions promoting life extension.
Publication Title
Deficiency of the lipid synthesis enzyme, DGAT1, extends longevity in mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We used microarrays to detail the global programme of gene expression underlying the loss of CD28 co-receptor on primary human CD8+ T cells.
Publication Title
Metabolic reprogramming of human CD8<sup>+</sup> memory T cells through loss of SIRT1.
Sample Metadata Fields
Age, Specimen part
View Samples- Oryza sativa
- 9 Downloadable Samples
- Affymetrix Rice Genome Array (rice)
Description
affy_xoo_rice - affy_xoo_rice - The Bacterial Leaf Blight disease of rice is due to Xanthomonas oryzae pv. oryzae. As for many pathogenic bacteria, it relies on a type 3 secretion system that is devoted to the injection of type 3 effectors into the eukaryotic host cell. These proteins are meant to suppress host basal defense responses and/or mimic some host regulatory function promoting bacterial survey in the plant. We are interested in the functional analysis of a subgroup of Xoo T3Es, that are specialized in host cell transcriptome remodelling. These effectors, therefore called TAL for Transcription Activator-Like proteins (also named AvrBs3/PthA-like), are often key virulence factors essential to Xoo pathogenicity such as the effector protein Talc of african Xoo strain BAI3. Our goal is to understand its function during disease development, by identifying rice host genes that are being directly up- or down-regulated by Talc. To that end, we aim at performing Affymetrix transcriptomic analysis, comparing leaf samples of a susceptible rice line inoculated with Xoo to leaves challenged with a Talc-deficient mutant and water-treated leaves. Highly induced genes are likely to be Talc primary targets and therefore potentially good susceptibility gene candidates.-The goal of the experiment is to identify the rice genes up- or down-regulated by the type III effector Talc from Xoo African strain BAI3, upon the inoculation of susceptible rice leaves 24 hours post-infection. To that end, the experimental design includes the inoculation of Nipponbare rice leaves with the virulent Xoo strain BAI3, that will be compared to Nipponbare rice leaves inoculated with a talc K.O. mutant strain and water.
Publication Title
Colonization of rice leaf blades by an African strain of Xanthomonas oryzae pv. oryzae depends on a new TAL effector that induces the rice nodulin-3 Os11N3 gene.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
SIRT3 is a mitochondrial NAD(+)-dependent protein deacetylase, which regulates the enzymatic activity of several mitochondrial proteins.
Publication Title
SIRT3 deficiency and mitochondrial protein hyperacetylation accelerate the development of the metabolic syndrome.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Brown Adipose YY1 Deficiency Activates Expression of Secreted Proteins Linked to Energy Expenditure and Prevents Diet-Induced Obesity.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples