The epigenetics of estrogen: Epigenetic regulation of hormone-induced memory enhancement

Epigenetic processes have been implicated in everything from cell proliferation to maternal behavior. Epigenetic alterations, including histone alterations and DNA methylation, have also been shown to play critical roles in the formation of some types of memory, and in the modulatory effects that factors, such as stress, drugs of abuse and environmental stimulation, have on the brain and memory function. Recently, we demonstrated that the ability of the sex-steroid hormone 17β-estradiol (E₂) to enhance memory formation is dependent on histone acetylation and DNA methylation, a finding that has important implications for understanding how hormones influence cognition in adulthood and aging. In this article, we provide an overview of the literature demonstrating that epigenetic processes and E₂ influence memory, describe our findings indicating that epigenetic alterations regulate E₂-induced memory enhancement, and discuss directions for future work on the epigenetics of estrogen.Key words: histone acetylation, DNA methylation, estradiol, cognition, hippocampusAn increasing body of evidence demonstrates a critical role of epigenetic processes in mediating complex psychological processes like learning and memory. Both histone alterations (e.g., acetylation, phosphorylation, methylation) and DNA methylation appear to play important roles in long-term memory formation, and recent work suggests that these epigenetic processes work synergistically to regulate memory.¹ In addition, factors that modulate memory formation, such as stress, drugs of abuse, depression and environmental stimulation, have been reported to influence the brain and cognitive function via epigenetic mechanisms,^2–5 suggesting that epigenetic alterations are critical for both basic memory formation and the modulatory influences of environmental experience and hormones. Recently, my lab has shown that the ability of sex-steroid hormones, specifically the potent estrogen 17β-estradiol (E₂), to enhance memory also depends on epigenetic mechanisms.⁶ This finding has important implications for understanding how sex-steroid hormones affect cognitive function in development, adulthood and aging, and it will be argued here that epigenetic alterations are critically important in mediating the effects of hormones on cognition. The sections that follow provide a brief overview of how epigenetic processes and E₂ independently influence memory, and then discuss the roles that epigenetic alterations play in regulating E₂-induced memory enhancement.