title: Conservation analysis of sequences flanking the testis-determining gene Sry in 17 mammalian species.
abstract: BACKGROUND
  Sex determination in mammals requires expression of the Y-linked gene Sry in the bipotential genital ridges of the XY embryo. Even minor delay of the onset of Sry expression can result in XY sex reversal, highlighting the need for accurate gene regulation during sex determination. However, the location of critical regulatory elements remains unknown. Here, we analysed Sry flanking sequences across many species, using newly available genome sequences and computational tools, to better understand Sry's genomic context and to identify conserved regions predictive of functional roles.
  
  
  METHODS
  Flanking sequences from 17 species were analysed using both global and local sequence alignment methods. Multiple motif searches were employed to characterise common motifs in otherwise unconserved sequence.
  
  
  RESULTS
  We identified position-specific conservation of binding motifs for multiple transcription factor families, including GATA binding factors and Oct/Sox dimers. In contrast with the landscape of extremely low sequence conservation around the Sry coding region, our analysis highlighted a strongly conserved interval of ~106 bp within the Sry promoter (which we term the Sry Proximal Conserved Interval, SPCI). We further report that inverted repeats flanking murine Sry are much larger than previously recognised.
  
  
  CONCLUSIONS
  The unusually fast pace of sequence drift on the Y chromosome sharpens the likely functional significance of both the SPCI and the identified binding motifs, providing a basis for future studies of the role(s) of these elements in Sry regulation.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
authors.forename: Christian
authors.initials: C
authors.lastname: Larney
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Bailey
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia. p.koopman@imb.uq.edu.au.
authors.forename: Peter
authors.initials: P
authors.lastname: Koopman
mesh_terms: D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D019143:Evolution, Molecular; D006801:Humans; D008322:Mammals / Q000145:classification / Q000235:genetics*; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D051876:Sex-Determining Region Y Protein / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors