CDYL reinforces male gonadal sex determination through epigenetically repressing transcription in mice.

In mammals, male and female gonads initially develop from bipotential progenitor cells, which can differentiate into either testicular or ovarian cells. The decision to adopt a testicular or ovarian fate relies on robust genetic forces, i.e., activation of the testis-determining gene , as well as a delicate balance of expression levels for pro-testis and pro-ovary factors. Recently, epigenetic regulation has been found to be a key element in activation of . Nevertheless, the mechanism by which epigenetic regulation controls the expression balance of pro-testis and pro-ovary factors remains unclear. Chromodomain Y-like protein (CDYL) is a reader protein for repressive histone H3 methylation marks. We found that a subpopulation of -deficient mice exhibited XY sex reversal. Gene expression analysis revealed that the testis-promoting gene was downregulated in XY -deficient gonads during the sex determination period without affecting expression. Instead, we found that the ovary-promoting gene was derepressed in XY -deficient gonads prior to and during the sex-determination period. heterozygous deficiency restored expression in -deficient XY gonads, indicating that derepressed is a cause of the repression of . We found that CDYL directly bound to the promoter and maintained its H3K27me3 levels during the sex-determination period. These findings indicate that CDYL reinforces male gonadal sex determination by repressing the ovary-promoting pathway in mice.