Axial (HNF3β) and retinoic acid receptors are regulators of the zebrafish sonic hedgehog promoter

• Published in: The EMBO journal Vol. 16; no. 13; pp. 3955 - 3964
• Main Authors: Chang, Bei-En, Blader, Patrick, Fischer, Nadine, Ingham, Philip W., Strähle, Uwe
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.07.1997; EMBO Press
• Subjects: Animals; axial (HNF3β); Base Sequence; Binding Sites; Biochemistry, Molecular Biology; Cloning, Molecular; DNA, Complementary; DNA-Binding Proteins - physiology; floor plate; Forkhead Transcription Factors; Freshwater; Gene Expression Regulation; Hedgehog Proteins; HeLa Cells; Hepatocyte Nuclear Factor 3-beta; Humans; Life Sciences; Molecular Sequence Data; notochord; Nuclear Proteins - physiology; Promoter Regions, Genetic; Proteins - genetics; Rats; Receptors, Retinoic Acid - physiology; retinoic acid; Retinoic Acid Receptor alpha; Retinoid X Receptors; sonic hedgehog; Trans-Activators; Transcription Factors - physiology; Transcriptional Activation; Zebrafish; Zebrafish Proteins
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1093/emboj/16.13.3955

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 (HNF3β 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 HNF3β in HeLa cells results in activation of co‐transfected sonic hedgehog promoter–CAT fusion genes. This effect is mediated by two Axial (HNF3β) 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 (HNF3β) and retinoic acid receptors are direct regulators of the sonic hedgehog gene.