GPER1 and neoplasm: On one hand, GPER governs epigenetic histone alterations (H3K4me3 and H3K27ac) to affect tumor progression,175,176 and sex-specific mechanisms are of utmost significance as the down-regulation of GPER is associated with promoter hypermethylation and reduced enrichment of H3K4me3 and H3K27ac marks around the GPER promoter.177