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- Title
Differential Control of Notch1 Gene Transcription by Klf4 and Sp3 Transcription Factors in Normal versus Cancer-Derived Keratinocytes.
- Authors
Lambertini, Chiara; Pantano, Serafino; Dotto, G. Paolo
- Abstract
In specific cell types like keratinocytes, Notch signaling plays an important pro-differentiation and tumor suppressing function, with down-modulation of the Notch1 gene being associated with cancer development. Besides being controlled by p53, little else is known on regulation of Notch1 gene expression in this context. We report here that transcription of this gene is driven by a TATA-less ''sharp peak'' promoter and that the minimal functional region of this promoter, which extends from the 2342 bp position to the initiation codon, is differentially active in normal versus cancer cells. This GC rich region lacks p53 binding sites, but binds Klf4 and Sp3. This finding is likely to be of biological significance, as Klf4 and, to a lesser extent, Sp3 are up-regulated in a number of cancer cells where Notch1 expression is down-modulated, and Klf4 overexpression in normal cells is sufficient to down-modulate Notch1 gene transcription. The combined knock-down of Klf4 and Sp3 was necessary for the reverse effect of increasing Notch1 transcription, consistent with the two factors exerting an overlapping repressor function through their binding to the Notch1 promoter.
- Subjects
GENETIC transcription; KERATINOCYTES; TRANSCRIPTION factors; CANCER invasiveness; GENE expression; GENETIC regulation; PROMOTERS (Genetics); CANCER cells; GENETIC repressors
- Publication
PLoS ONE, 2010, Vol 5, Issue 4, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0010369