title: Global genome analysis of the downstream binding targets of testis determining factor SRY and SOX9.
abstract: A major event in mammalian male sex determination is the induction of the testis determining factor Sry and its downstream gene Sox9. The current study provides one of the first genome wide analyses of the downstream gene binding targets for SRY and SOX9 to help elucidate the molecular control of Sertoli cell differentiation and testis development. A modified ChIP-Chip analysis using a comparative hybridization was used to identify 71 direct downstream binding targets for SRY and 109 binding targets for SOX9. Interestingly, only 5 gene targets overlapped between SRY and SOX9. In addition to the direct response element binding gene targets, a large number of atypical binding gene targets were identified for both SRY and SOX9. Bioinformatic analysis of the downstream binding targets identified gene networks and cellular pathways potentially involved in the induction of Sertoli cell differentiation and testis development. The specific DNA sequence binding site motifs for both SRY and SOX9 were identified. Observations provide insights into the molecular control of male gonadal sex determination.
authors.affiliation: Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, Washington, United States of America.
authors.forename: Ramji K
authors.initials: RK
authors.lastname: Bhandari
authors.forename: Md M
authors.initials: MM
authors.lastname: Haque
authors.forename: Michael K
authors.initials: MK
authors.lastname: Skinner
mesh_terms: D000818:Animals; D001483:Base Sequence; D047369:Chromatin Immunoprecipitation; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks / Q000235:genetics; D016678:Genome / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D059372:Nucleotide Motifs / Q000235:genetics; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D055758:SOX9 Transcription Factor / Q000378:metabolism*; D019849:Sex Determination Processes / Q000235:genetics*; D051876:Sex-Determining Region Y Protein / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D013737:Testis / Q000378:metabolism*
chemical_list: D055758:SOX9 Transcription Factor; D051876:Sex-Determining Region Y Protein; C497747:Sry protein, rat