Title: Direct regulation of the Nrarp gene promoter by the Notch signaling pathway
Authors: Pirot, Pierre ×
Van Grunsven, Leonardus
Marine, Chris
Huylebroeck, Danny
Bellefroid, Eric J #
Issue Date: Aug-2004
Series Title: Biochemical and Biophysical Research Communications vol:322 issue:2 pages:526-34
Abstract: Nrarp encodes for an evolutionarily conserved small ankyrin repeat-containing protein that functions as a negative regulator of Notch signaling. Interestingly, increased Nrarp transcription was observed following induction of Notch signaling, suggesting the existence of a negative feedback loop. We show here that both mouse and human promoter regions of Nrarp share two conserved regions located approximately 2 and approximately 3 kb upstream of the transcription start site each containing a perfect putative binding site for the Notch-dependent transcription factor Su(H). A 4.4 kb genomic fragment of the mouse Nrarp locus containing those conserved regions and fused to a luciferase reporter gene showed basal promoter activity in 293T cells and this activity was strongly increased by the intracellular domain of Notch, NICD. NICD-dependent stimulation was attenuated by a dominant negative mutant of Su(H), Su(H)DBM, and was not observed in Su(H)-deficient cells (OT-11). Promoter bashing and gel shift assays revealed that the most distal putative Su(H) binding site located within the -3 kb conserved element plays a crucial role in this induction. Collectively, these results provide definitive support for direct regulation of the Nrarp gene by the Notch pathway.
ISSN: 0006-291X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Biology (Celgen) (-)
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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