that higher powered experiments may identify additional genomic regions of E2-responsive DNA methylation change in the hippocampus. The findings of enriched SP-1 binding sites and increased evidence for hippocampal long-term potentiation-associated genes in E2-responsive DMRs is consistent with the known downstream transcription factor activation32–35 as well as antidepressant functions of E2 exposure in the hippocampus,36 and adds confidence to the assertion that we are detecting true E2 DMRs.