Figure 4.

An epigenetic switch in puberty. At puberty onset, GnRH expressing neurons, residing in the preoptic area and hypothalamus, release GnRH in a tightly controlled fashion from their axon terminals into the median eminence. The capillary plexus in the upper infundibulum transports GnRH to the anterior pituitary to stimulate luteinizing hormone (LH) secretion. A surge in LH release is necessary to induce ovulation, and subsequent estradiol production feeds back to GnRH neurons. Kisspeptin derived from kisspeptin/neurokinin B/dynorphin (KNDy) expressing neurons stimulate GnRH neurons. During prepubertal age, polycomb complexes (comprising the factors eed, cbx7, and yy1) occupy Kiss1 and confer silencing. As puberty draws near, dynamic hypermethylation of eed and cbx7 leads to a decrease in repressive (H3K27me3) histone marks in favor of an increase in active ones (H3K9/14ac, H3K4me3) and tilts balanced inhibition towards Kiss1 activation, polymerase II (PolII) driven transcription, and puberty onset.