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Advances in molecular biology have provided tools for studying the epigenetic factors that modulate gene expression. DNA methylation is an epigenetic modification that can have sustained effects on transcription and is associated with long-term gene silencing. In this review, we focus on the regulation of estrogen receptor alpha (ERα) expression by hormonal and environmental cues, the consequences of these cues for female maternal and sexual behavior, and recent studies that explore the role of DNA methylation in mediating these developmental effects, with particular focus on the mediating role of maternal care. The methylation status of ERα has implications for reproductive behavior, cancer susceptibility, and recovery from ischemic injury, suggesting an epigenetic basis for risk and resilience across the life span.