An upstream regulatory element of the NCAM promoter contains a binding site for homeodomains.
In the present study, we have analyzed an upstream regulatory element of the neural cell adhesion molecule (NCAM) promoter which is required for full promoter activity. It contains an ATTATTA motif that resembles the core recognition sequence of homeodomain (HD) proteins of the Antennapedia (Antp) and related types. Electrophoretic mobility shift (EMSA) and DNase I footprinting analyses revealed that the Drosophila HDs coded by the Antp and the zerknüllt (zen) genes bind this site in vitro. In contrast, the engrailed (en) protein did not produce a detectable footprint. The functional relevance of the ATTATTA motif was demonstrated by showing that a two-nucleotide exchange curtailed stimulation of an heterologous promoter. An oligonucleotide known to be recognized with high affinity by Antp-like HDs efficiently competed for endogenous factor binding. These results suggest that the NCAM gene may be a target for HD proteins.
Hirsch
M R
MR
Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, France.
Valarché
I
I
Deagostini-Bazin
H
H
Pernelle
C
C
Joliot
A
A
Goridis
C
C
D000818:Animals; D051943:Antennapedia Homeodomain Protein; D001483:Base Sequence; D001665:Binding Sites; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins; D005801:Genes, Homeobox; D018398:Homeodomain Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors
D051943:Antennapedia Homeodomain Protein; C497974:Antp protein, Drosophila; D015816:Cell Adhesion Molecules, Neuronal; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors