It is thus apparent that the genetic underpinnings of puberty are multigenic, but this realization does not explain how inherited, permanent changes in DNA sequence can regulate gene expression dynamically, while also imposing an encompassing level of coordination and transcriptional plasticity to the gene networks involved. Here we develop the concept that a biological regulatory system that meets these requirements is epigenetics. Our results provide proof-of-principle for the view that the timing of female puberty is under the regulatory control of an epigenetic mechanism of transcriptional repression. We identify the Polycomb group (PcG) of transcriptional silencers 20 as integral parts of this repressive mechanism, and implicate two PcG genes (Cbx7 and Eed) as core components of the PcG complex operating in the prepubertal hypothalamus. Using the Kiss1 gene as a prototype of a gene whose products are directly involved in controlling GnRH output 21, we provide evidence for the view that the PcG complex represses the advent of reproductive maturity by targeting downstream genes involved in the stimulatory control of GnRH secretion at puberty.
