GEO DataSets

(Submitter supplied) Notch is needed for T cell development and is a common oncogenic driver in T cell acute lymphoblastic leukemia. Myc is a critical target of Notch in normal and malignant pre-T cells, but how Notch regulates Myc is unknown. Here, we identify a distal enhancer located >1 Mb 3' of human and murine Myc that binds Notch transcription complexes and physically interacts with the Myc proximal promoter. The Notch1 binding element in this region activates reporter genes in a Notch-dependent, cell context-specific fashion that requires a conserved Notch complex binding site. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL9185

9 Samples

Download data: BED

(Submitter supplied) The main oncogenic driver in T-lymphoblastic leukemia (T-LL) is NOTCH1, which activates genes by forming chromatin-associated Notch transcription complexes. Gamma-secretase (GSI) inhibitor treatment prevents NOTCH1 nuclear localization, but most genes with NOTCH1 binding sites are insensitive to GSI. Here, we demonstrate that fewer than 10% of NOTCH1 binding sites show dynamic changes in NOTCH1 occupancy when T-LL cells are toggled between the Notch-on and –off states with GSI. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL11154

15 Samples

Download data: BED

(Submitter supplied) ChIP-Seq detected global binding of NOTCH1 oncogene in a human T-Cell Leukemia Cell line.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL9442

2 Samples

Download data: BED, BEDGRAPH

(Submitter supplied) Analysis of Gene Expression in KO mice lacking the NOTCH1-bound MYC putative enhancer located at +1.43K downstream of the MYC gene. Enrichment of MYC signature genes were analyzed by GSEA. Results show that MYC expression signature is indeed significantly enriched.

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL6887

6 Samples

Download data: TXT

(Submitter supplied) Notch1 regulates gene expression by associating with the DNA-binding factor RBPJ and is oncogenic in murine and human T cell progenitors. Using ChIP-Seq, we find that in human and murine T-LL genomes Notch1 binds preferentially to promoters, to RBPJ binding sites, and near imputed ZNF143, Ets and Runx sites. ChIP-Seq confirmed that ZNF143 binds to ~40% of Notch1 sites. Notch1/ZNF143 sites are characterized by high Notch1 and ZNF143 signals, frequent co-binding of RBPJ (generally through sites embedded within ZNF143 motifs), strong promoter bias, and relatively low mean levels of activating chromatin marks. more...

Organism:

Homo sapiens; Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL9052 GPL9185

16 Samples

Download data: BED

(Submitter supplied) Notch is normally activated by cleavage and nuclear translocation of its intracellular domain (ICN1), which turns on downstream target genes. Human T cell acute lymphoblastic leukemia (T-ALL), an aggressive immature T cell malignancy, is associated with Notch 1 gain-of-function mutations in more than 50% of the cases. Efforts to date to identify direct Notch1 targets have been confounded by the lack of a method to turn Notch1 on in a controlled fashion in T-ALL cells that are poised to respond to Notch signals. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Dataset:

GDS4289

Platform:

GPL570

45 Samples

Download data: CEL

Analysis of Notch1-dependent TLL cell line CUTLL1 treated with γ-secretase-inhibitor (GSI) to block Notch signaling, subjected to GSI washout to induce Notch1 reactivation, and incubated up to 4hr with translational inhibitor cycloheximide. Results provide insight into Notch1 function in TLL.

Organism:

Homo sapiens

Type:

Expression profiling by array, transformed count, 3 agent, 3 cell line, 7 protocol sets

Platform:

GPL570

Series:

GSE29544

45 Samples

Download data: CEL

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by array; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL570 GPL11154

36 Samples

Download data: BW, CEL

(Submitter supplied) Here we modeled T-ALL resistance to Notch inhibition, identifying ‘persister’ cells that readily expand in the presence of gamma secretase inhibitor (GSI) and the absence of Notch signaling. Rare persister cells are already present in naïve T-ALL populations, and the reversibility of the phenotype is suggestive of an epigenetic mechanism. Relative to GSI-sensitive cells, persisters activate distinct signaling and gene expression programs, and exhibit global chromatin compaction. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL11154

28 Samples

Download data: BW

(Submitter supplied) Here we modeled T-ALL resistance to Notch inhibition, identifying ‘persister’ cells that readily expand in the presence of gamma secretase inhibitor (GSI) and the absence of Notch signaling. Rare persister cells are already present in naïve T-ALL populations, and the reversibility of the phenotype is suggestive of an epigenetic mechanism. Relative to GSI-sensitive cells, persisters activate distinct signaling and gene expression programs, and exhibit global chromatin compaction. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

8 Samples

Download data: CEL

(Submitter supplied) Oncogenic driver mutations are those that provide a proliferative or survival advantage to neoplastic cells resulting in clonal selection. Although most cancer causing mutations have been detected in the protein-­coding regions of the cancer genome, driver mutations have recently also been discovered within noncoding genomic sequences. Thus, a current challenge is to gain precise understanding of how these unique genomic elements function in cancer pathogenesis, while clarifying mechanisms of gene regulation and identifying new targets for therapeutic intervention. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL16791

1 Sample

Download data: WIG

(Submitter supplied) RNA-seq of control, shARIEL Jurkat cells

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20301

4 Samples

Download data: TXT

(Submitter supplied) Human T-cell Acute lymphoblastic Leukemia cell line CEM was transfected with either shRNA against ZMIZ1 or scrambled shRNA. Four (non-paired) biological replicates of each condition had mRNA assays performed using Affymetrix HG_U133_plus_2 arrays, with 54675 probe-sets. A supplementary Excel workbook holding the same processed data as the series matrix file is provided, with some probe set annotation, and a simple statistical comparison. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

8 Samples

Download data: CEL, XLS

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by array; Expression profiling by high throughput sequencing

Platforms:

GPL11154 GPL19197

144 Samples

Download data: TXT

(Submitter supplied) Genetic studies in T-cell acute lymphoblastic leukemia have uncovered a remarkable complexity of oncogenic and loss-of-function mutations. Amongst this plethora of genetic changes, NOTCH1 activating mutations stand out as the most frequently occurring genetic defect, identified in more than 50% of T-cell acute lymphoblastic leukemias, supporting an essential driver role for this gene in T-cell acute lymphoblastic leukemia oncogenesis. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

4 Samples

Download data: TSV

(Submitter supplied) Genetic studies in T-cell acute lymphoblastic leukemia have uncovered a remarkable complexity of oncogenic and loss-of-function mutations. Amongst this plethora of genetic changes, NOTCH1 activating mutations stand out as the most frequently occurring genetic defect, identified in more than 50% of T-cell acute lymphoblastic leukemias, supporting an essential driver role for this gene in T-cell acute lymphoblastic leukemia oncogenesis. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

12 Samples

Download data: TSV

(Submitter supplied) Genetic studies in T-cell acute lymphoblastic leukemia have uncovered a remarkable complexity of oncogenic and loss-of-function mutations. Amongst this plethora of genetic changes, NOTCH1 activating mutations stand out as the most frequently occurring genetic defect, identified in more than 50% of T-cell acute lymphoblastic leukemias, supporting an essential driver role for this gene in T-cell acute lymphoblastic leukemia oncogenesis. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL19197

13 Samples

Download data: TXT

(Submitter supplied) Genetic studies in T-cell acute lymphoblastic leukemia have uncovered a remarkable complexity of oncogenic and loss-of-function mutations. Amongst this plethora of genetic changes, NOTCH1 activating mutations stand out as the most frequently occurring genetic defect, identified in more than 50% of T-cell acute lymphoblastic leukemias, supporting an essential driver role for this gene in T-cell acute lymphoblastic leukemia oncogenesis. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL19197

8 Samples

Download data: TXT

(Submitter supplied) Genetic studies in T-cell acute lymphoblastic leukemia have uncovered a remarkable complexity of oncogenic and loss-of-function mutations. Amongst this plethora of genetic changes, NOTCH1 activating mutations stand out as the most frequently occurring genetic defect, identified in more than 50% of T-cell acute lymphoblastic leukemias, supporting an essential driver role for this gene in T-cell acute lymphoblastic leukemia oncogenesis. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL19197

16 Samples

Download data: TXT

(Submitter supplied) Genetic studies in T-cell acute lymphoblastic leukemia have uncovered a remarkable complexity of oncogenic and loss-of-function mutations. Amongst this plethora of genetic changes, NOTCH1 activating mutations stand out as the most frequently occurring genetic defect, identified in more than 50% of T-cell acute lymphoblastic leukemias, supporting an essential driver role for this gene in T-cell acute lymphoblastic leukemia oncogenesis. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL19197

12 Samples

Download data: TXT