title: Dax1 expression is dependent on steroidogenic factor 1 in the developing gonad.
abstract: The nuclear hormone receptor DAX1 has been implicated in mammalian gonad development and sex determination. The expression of the gene in the gonad follows a dynamic pattern in time and place in the embryo and the adult. We have undertaken the first in vivo study of the regulation of Dax1 expression. Using a transgenic mouse approach we have identified a novel 500-bp region 4 kb upstream of the mouse Dax1 start codon that is essential for LacZ reporter gene expression in the embryonic gonad. Within this region, a highly conserved steroidogenic factor 1 (SF1) consensus-binding site is necessary to direct LacZ expression to the embryonic gonad implicating SF1 in the regulation of Dax1 in the developing gonad. Consistent with this, Dax1 is expressed at much reduced levels in gonads of embryos that are deficient in SF1. In addition, our results show that SF1 consensus-binding sites close to the start of Dax1 transcription are important in regulating levels of expression in the developing gonad. These studies have identified the critical in vivo regulatory region for expression of Dax1 in the early gonad and provide novel information on how a specific enhancer element acts in different cell types at different stages of development.
authors.affiliation: Section of Gene Function and Regulation, Chester Beatty Laboratories, Institute of Cancer Research, London SW3 6JB.
authors.forename: Christine
authors.initials: C
authors.lastname: Hoyle
authors.forename: Veronica
authors.initials: V
authors.lastname: Narvaez
authors.forename: Graham
authors.initials: G
authors.lastname: Alldus
authors.forename: Robin
authors.initials: R
authors.lastname: Lovell-Badge
authors.forename: Amanda
authors.initials: A
authors.lastname: Swain
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D018387:Codon, Initiator; D016384:Consensus Sequence; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D051717:Fushi Tarazu Transcription Factors; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D006066:Gonads / Q000196:embryology*; D018398:Homeodomain Proteins; D006801:Humans; D007763:Lac Operon; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis* / Q000235:genetics; D012097:Repressor Proteins; D016415:Sequence Alignment; D054339:Steroidogenic Factor 1; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*
chemical_list: D018387:Codon, Initiator; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; C539965:NR0B1 protein, human; C515057:NR5A1 protein, human; C539966:Nr0b1 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; C515058:steroidogenic factor 1, mouse