title: The sex-determining factors SRY and SOX9 regulate similar target genes and promote testis cord formation during testicular differentiation.
abstract: Male sex determination is mediated sequentially by sex-determining region Y (SRY) and related SRY-box 9 (SOX9) transcription factors. To understand the gene regulatory hierarchy for SRY and SOX9, a series of chromatin immunoprecipitation and whole-genome promoter tiling microarray (ChIP-Chip) experiments were conducted with mouse gonadal cells at the time of sex determination. SRY and SOX9 bind to the promoters of many common targets involved in testis differentiation and regulate their expression in Sertoli cells. SRY binds to various ovarian differentiation genes and represses their activation through WNT/β-catenin signaling. Sertoli cell-Sertoli cell junction signaling, important for testis cord formation, is the top canonical pathway among the SRY and SOX9 targets. Hence, SRY determines Sertoli cell fate by repressing ovarian and activating testicular differentiation genes, promotes early Sertoli cells to form testis cord, and then passes on its functions to SOX9, which regulates common targets and activates its own gene regulatory program, beyond SRY actions, in sex determination.
authors.affiliation: Laboratory of Cell and Developmental Genetics, Department of Medicine, VA Medical Center, University of California, San Francisco, San Francisco, CA 94121, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Yunmin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, Palo Alto, CA 94305, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Laboratory of Cell and Developmental Genetics, Department of Medicine, VA Medical Center, University of California, San Francisco, San Francisco, CA 94121, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: chris.lau@ucsf.edu.
authors.forename: Yun-Fai Chris
authors.initials: YF
authors.lastname: Lau
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D012708:Sertoli Cells / Q000166:cytology* / Q000378:metabolism; D019849:Sex Determination Processes; D051876:Sex-Determining Region Y Protein / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: D055758:SOX9 Transcription Factor; D051876:Sex-Determining Region Y Protein; C527933:Sox9 protein, mouse