title: The molecular action and regulation of the testis-determining factors, SRY (sex-determining region on the Y chromosome) and SOX9 [SRY-related high-mobility group (HMG) box 9].
abstract: Despite 12 yr since the discovery of SRY, little is known at the molecular level about how SRY and the SRY-related protein, SOX9 [SRY-related high-mobility group (HMG) box 9], initiate the program of gene expression required to commit the bipotential embryonic gonad to develop into a testis rather than an ovary. Analysis of SRY and SOX9 clinical mutant proteins and XX mice transgenic for testis-determining genes have provided some insight into their normal functions. SRY and SOX9 contain an HMG domain, a DNA-binding motif. The HMG domain plays a central role, being highly conserved between species and the site of nearly all missense mutations causing XY gonadal dysgenesis. SRY and SOX9 are architectural transcription factors; their HMG domain is capable of directing nuclear import and DNA bending. Whether SRY and SOX9 activate testis-forming genes, repress ovary-forming genes, or both remains speculative until downstream DNA target genes are identified. However, factors that control SRY and SOX9 gene expression have been identified, as have a dozen sex-determining genes, allowing some of the pieces in this molecular genetic puzzle to be connected. Many genes, however, remain unidentified, because in the majority of cases of XY females and in all cases of XX males lacking SRY, the mutated gene is unknown.
authors.affiliation: Prince Henry's Institute of Medical Research, Clayton 3168, Victoria, Australia. Vincent.harley@med.monash.edu.au
authors.forename: Vincent R
authors.initials: VR
authors.lastname: Harley
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Clarkson
authors.forename: Anthony
authors.initials: A
authors.lastname: Argentaro
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D012734:Disorders of Sex Development; D005260:Female; D005786:Gene Expression Regulation; D024742:HMG-Box Domains / Q000235:genetics / Q000502:physiology; D006609:High Mobility Group Proteins / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009687:Nuclear Proteins; D038081:Organogenesis / Q000235:genetics / Q000502:physiology; D055758:SOX9 Transcription Factor; D016415:Sequence Alignment; D012733:Sex Differentiation; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014998:Y Chromosome / Q000235:genetics / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D009687:Nuclear Proteins; D055758:SOX9 Transcription Factor; D051876:Sex-Determining Region Y Protein; C527933:Sox9 protein, mouse; C497746:Sry protein, mouse; D014157:Transcription Factors