Pax3 regulates Wnt1 expression via a conserved binding site in the 5' proximal promoter.
The development of the neural crest is orchestrated by a complex interplay between intercellular signalling molecules and transcription factors. Here, we demonstrate a direct interaction between two such factors, the paired-type transcription factor Pax3 and the secretory glycoprotein Wnt1. We found that the Wnt1 promoter can be regulated by Pax3 in a dose-dependent manner. Sequence analysis predicted a conserved binding site for Pax3 within the Wnt1 promoter region. Deletion or mutation of this sequence abolished the promoter response to Pax3. Using chromatin immunoprecipitation (ChIP) assays, we demonstrated that Pax3 interacts with the Wnt1 promoter in vivo. These data indicate that Pax3 directly regulates the expression of Wnt1 in the developing embryo.
Fenby
Benjamin T
BT
Genes and Development Group, Centres for Integrative Physiology and Neuroscience Research, School of Biomedical Sciences, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh, EH8 9XD, UK.
Fotaki
Vassiliki
V
Mason
John O
JO
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D015536:Down-Regulation; D047108:Embryonic Development / Q000235:genetics; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008817:Mice, Mutant Strains; D009432:Neural Crest / Q000196:embryology*; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051155:Wnt1 Protein / Q000235:genetics*
D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; C068686:Pax3 protein, mouse