Because the kisspeptin-GPR54 system is critical for both puberty and adult reproductive function 15, 16, the Kiss1 gene can be considered as a prototype of the class of genes that need to be activated for puberty to occur. Accordingly, we used the Kiss1 gene to test the hypothesis that these puberty activating genes may be subjected to PcG repressive control. The increase in Kiss1 mRNA abundance that occur in the hypothalamus at the time of puberty was prevented, instead of enhanced by inhibition of DNA methylation, suggesting that a secondary mechanism set in motion by the loss of DNA methylation is responsible for the reduction in Kiss1 expression. A significant component of this mechanism appears to be the PcG silencing complex as the prepubertal association of EED to the Kiss1 promoter, which diminishes at the onset of puberty, is prevented by inhibition of DNA methylation.
