Systematic name M39016
Brief description Genes upregulated by rapid Notch activation and linked to Notch TF binding peaks in mantle cell lymphoma cell lines.
Full description or abstract Gain-of-function Notch mutations are recurrent in mature small B cell lymphomas such as mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). We identified Notch-activated genes via rapid washout of gamma secretase inhibitor in MCL cell lines with activating Notch gene rearrangements, or that had been pre-stimulated by immobilized Notch ligand. We performed integrative analysis of Notch-regulated transcripts, genomic binding of Notch transcription factor complexes, and genome conformation data to identify direct Notch target genes in MCL cell lines. Likely indirect target genes (MYC-activated genes) were excluded by Notch activation experiments conducted in a cell line in which MYC expression was independent of Notch due to a genomic rearrangement of the MYC locus. This B cell Notch regulome is largely controlled through Notch-bound distal enhancers and includes genes involved in B cell receptor and cytokine signaling. We show that the oncogene MYC sustains proliferation of Notch-dependent MCL cell lines via a Notch-regulated lineage-restricted enhancer complex. Expression of direct Notch target genes is associated with Notch activity in an MCL xenograft model and in CLL lymph node biopsies.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 29045844   Authors: Ryan RJH,Petrovic J,Rausch DM,Zhou Y,Lareau CA,Kluk MJ,Christie AL,Lee WY,Tarjan DR,Guo B,Donohue LKH,Gillespie SM,Nardi V,Hochberg EP,Blacklow SC,Weinstock DM,Faryabi RB,Bernstein BE,Aster JC,Pear WS
Exact source Table S4. Linkage Analysis for Notch-Activated Genes and Notch Transcription Complex Binding Peaks in MCL Cell Lines; Tab 1; Column A
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Source species Homo sapiens
Contributed by Russell Ryan (University Of Michigan)
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