title: Axial (HNF3beta) and retinoic acid receptors are regulators of the zebrafish sonic hedgehog promoter.
abstract: The signalling molecule Sonic hedgehog is involved in a multitude of distinct patterning processes during vertebrate embryogenesis. In the nascent body axis of the zebrafish embryo, sonic hedgehog is co-expressed with axial (HNF3beta in mammals), a transcription regulator of the winged helix family. We show here that misexpression of axial leads to ectopic activation of sonic hedgehog expression in the zebrafish, suggesting that axial is a regulator of sonic hedgehog transcription. The sonic hedgehog gene was cloned from zebrafish and its promoter was characterized with respect to activation by axial. Expression of axial or rat HNF3beta in HeLa cells results in activation of co-transfected sonic hedgehog promoter-CAT fusion genes. This effect is mediated by two Axial (HNF3beta) recognition sequences. We furthermore identified a retinoic acid response element (RARE) in the sonic hedgehog upstream region which can be bound by retinoic acid receptor (RAR) and retinoid X receptor (RXR) heterodimers in vitro and confers retinoic acid inducibility to the sonic hedgehog promoter in the HeLa cell system. Our results suggest that both Axial (HNF3beta) and retinoic acid receptors are direct regulators of the sonic hedgehog gene.
authors.affiliation: IGBMC, CNRS/INSERM/ULP, BP 163, Illkirch, France.
authors.forename: B E
authors.initials: BE
authors.lastname: Chang
authors.forename: P
authors.initials: P
authors.lastname: Blader
authors.forename: N
authors.initials: N
authors.lastname: Fischer
authors.forename: P W
authors.initials: PW
authors.lastname: Ingham
authors.forename: U
authors.initials: U
authors.lastname: Strähle
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000502:physiology; D051858:Forkhead Transcription Factors; D005786:Gene Expression Regulation; D006367:HeLa Cells; D053823:Hedgehog Proteins; D051542:Hepatocyte Nuclear Factor 3-beta; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000502:physiology; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D051381:Rats; D018168:Receptors, Retinoic Acid / Q000502:physiology*; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D015534:Trans-Activators; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation; D015027:Zebrafish; D029961:Zebrafish Proteins
chemical_list: D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C496502:FOXA2 protein, human; D051858:Forkhead Transcription Factors; C496504:Foxa2 protein, rat; D053823:Hedgehog Proteins; D009687:Nuclear Proteins; D011506:Proteins; C000607071:RARA protein, human; C000607073:Rara protein, rat; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; C509239:SHH protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D029961:Zebrafish Proteins; C082243:foxa2 protein, zebrafish; C082925:retinoic acid receptor beta; D051542:Hepatocyte Nuclear Factor 3-beta