Activated Notch1 target genes during embryonic cell differentiation depend on the cellular context and include lineage determinants and inhibitors.

PloS One
Franziska Meier-StiegenUrsula Just

Abstract

Notch receptor signaling controls developmental cell fates in a cell-context dependent manner. Although Notch signaling directly regulates transcription via the RBP-J/CSL DNA binding protein, little is known about the target genes that are directly activated by Notch in the respective tissues. To analyze how Notch signaling mediates its context dependent function(s), we utilized a Tamoxifen-inducible system to activate Notch1 in murine embryonic stem cells at different stages of mesodermal differentiation and performed global transcriptional analyses. We find that the majority of genes regulated by Notch1 are unique for the cell type and vary widely dependent on other signals. We further show that Notch1 signaling regulates expression of genes playing key roles in cell differentiation, cell cycle control and apoptosis in a context dependent manner. In addition to the known Notch1 targets of the Hes and Hey families of transcriptional repressors, Notch1 activates the expression of regulatory transcription factors such as Sox9, Pax6, Runx1, Myf5 and Id proteins that are critically involved in lineage decisions in the absence of protein synthesis. We suggest that Notch signaling determines lineage decisions and expansion of stem c...Continue Reading

Associated Datasets

Jul 13, 2010·Ursula JustRalf Schwanbeck

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Datasets Mentioned

BETA
GSE15268

Methods Mentioned

BETA
nuclear translocation
flow cytometry
gene array
PCA
FACS
FCS

Software Mentioned

âTranscription Element Search Systemâ TESS
dChip
DAVID
MeV
R
TM4

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