github link
Accession IconGSE29544

Expression profiling of human T-LL cell line CUTLL1

Organism Icon Homo sapiens
Sample Icon 45 Downloadable Samples
Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Submitter Supplied Information

Description
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. Of note, because Notch signaling activates transcriptional repressors that feedback to dampen the expression of many target genes (a process referred to as incoherent logic), it is likely that many direct targets are missed in Notch off analyses, which are further complicated by an inability to identify direct targets in a clear-cut fashion. We have overcome this limitation by developing a GSI washout method that results in the rapid translocation of activated Notch1 to the nucleus. We intend to use this method to study the assembly and loading of transcriptional complexes onto downstream targets, the kinetics of target activation. To date, our efforts have been devoted to comparing the gene expression signature of Notch-on and Notch-off in the human T-ALL cell line CUTLL. In addition to previously identified Notch1 target genes, we have also identified a series of novel genes upregulated by GSI washout in the presence of cycloheximide, suggesting that they are likely to be direct targets.
PubMed ID
Total Samples
45
Submitter’s Institution
Alternate Accession IDs

Samples

Show of 0 Total Samples
Filter
Add/Remove
Accession Code
Title
Cell line
Processing Information
Additional Metadata
No rows found
Loading...