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Publication : Binding and activation of the promoter for the neural cell adhesion molecule by Pax-8.

First Author  Holst BD Year  1994
Journal  J Biol Chem Volume  269
Issue  35 Pages  22245-52
PubMed ID  8071351 Mgi Jnum  J:19968
Mgi Id  MGI:68087 Doi  10.1016/s0021-9258(17)31783-0
Citation  Holst BD, et al. (1994) Binding and activation of the promoter for the neural cell adhesion molecule by Pax-8. J Biol Chem 269(35):22245-52
abstractText  The neural cell adhesion molecule (N-CAM), is expressed in definite spatiotemporal patterns during development. To identify factors that may influence place-dependent n-cam gene expression, we have studied the binding and activation of the n-cam promoter by Pax-8, a member of the Pax family of transcription factors. Pax-8 increased n-cam promoter activity 13.4-fold in cellular co-transfection experiments, and a short segment of the promoter (-143 to -15) mediated the response. This region of the n-cam promoter produced a DNA-protein complex when incubated with either extracts from COS-7 cells transfected with the Pax-8 expression vector or a Pax-8/GST fusion protein. Pax-8 bound to the n-cam promoter through two TGCTCC motifs (designated PBS-1 and PBS-2) that resemble paired domain binding sites. Mutation of PBS-1 and PBS-2 eliminated Pax-8 activation of the n-cam promoter. Transfection of N2A neuroblastoma cells with the Pax-8 expression vector resulted in a 5-fold increase in the transcription of the endogenous n-cam gene. The combined results suggest that Pax-8 activates transcription of the n-cam gene through binding of sequences resembling paired domain binding sites in the n-cam promoter. The data raise the possibility that the n-cam promoter may be regulated by other members of the Pax gene family.
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