Promoter-specific regulation of gene expression by an exogenously added homedomain that promotes neurite growth.
pAntp, a 60 amino acid long peptide corresponding to the homeodomain of the Drosophila Antennapedia protein, translocates through neuronal membranes when added exogenously to neurons in culture, where it accumulates in the nucleus and promotes neurite outgrowth. We proposed that the peptide, once internalized, may compete for homeoprotein DNA binding sites. To investigate this point, we have produced a permanent fibroblast cell line which carries a luciferase reporter gene under the control of a 93 bp genomic region of the HOXD9 promoter with binding sites for homeoproteins. Externally added pAntp specifically down-regulates the expression of the reporter gene, suggesting that the neurotrophic effects observed previously are mediated by direct binding of pAntp to homeoprotein target sites.
Le Roux
I
I
CNRS URA 1414, Ecole Normale Supérieure, Paris, France.
Duharcourt
S
S
Volovitch
M
M
Prochiantz
A
A
Ronchi
E
E
D000818:Animals; D051943:Antennapedia Homeodomain Protein; D001692:Biological Transport; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D005801:Genes, Homeobox / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D018398:Homeodomain Proteins; D007739:L Cells; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D016501:Neurites; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014157:Transcription Factors; D015533:Transcriptional Activation; D014162:Transfection
D051943:Antennapedia Homeodomain Protein; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C490282:Hoxd9 protein, mouse; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D008156:Luciferases