examined the association of H3K4me3 to the Kiss1 promoter at mid-puberty, and found it to remain as elevated as in LJ. This developmental profile is consistent with the pattern of bivalent association observed for H3K27me3 and H3K4me3 in the promoter of genes mildly de-repressed during development 48. The evolving presence of both marks on the Kiss1 promoter at puberty is also consistent with the concept of “bivalent” domains 48, i.e., the simultaneous presence of repressive and activating histone modifications 48, 49 in the regulatory region of genes thought to be poised for activation in response to developmental cues 50. Noteworthy, the pubertal increase in the association of activating histone marks to the Kiss1 promoter failed to occur in Aza treated rats. Because the pubertal EED eviction also fails to occur in these animals, the simplest explanation is that persistent EED occupancy diminishes accessibility of activating histone marks to the Kiss1 promoter.
