XY for male? Not always

It is a well-known fact that the composition of the sex chromosomes determines biological gender. In mammals, individuals carrying XX chromosomes will be females, while individuals with XY chromosomes will be males, since the Y chromosome contains the genes Sox9 and Sry, which are responsible for embryonic male development. There is, however, more to the story. In an article published in the journal Nucleic Acids Research, Dr. Nitzan Gonen and her team focus on a specific genetic component on the Y chromosome, a non-coding DNA region called Enh13. Enh13 is an enhancer of the Sox9 gene, meaning that it enables Sox9 expression in the embryo. When specific critical elements in Enh13 are deleted, the Sox9 expression is significantly diminished, leading to a female-like phenotype in an embryo carrying XY chromosomes. Interestingly, this provides a molecular explanation for distinct clinical outcomes observed in patients harboring different variants in Enh13.