Sex determination involves synergistic action of SRY and SF1 on a specific Sox9 enhancer

The Sry gene, first cloned in 1990, was proven by mutation studies and sex reversal in transgenic mice to be the Y-linked mammalian testis-determining gene. Many other genes have since been implicated in early gonad development and in the decision to make testes or ovaries, but no proven direct target of SRY had been identified. Now a study of gene expression patterns in developing mouse embryos shows that the product of Sry, the testis-determining factor SRY, forms a complex with an orphan nuclear receptor SF1, and together they bind to an enhancer regulating Sox9, which is known to control the expression of genes involved in male development. Earlier work had suggested through studies of genetic interactions that Sox9 is a target of SRY. However, this study for the first time identifies a direct regulatory interaction at the level of transcriptional regulation, and identifies the enhancer element responsible.