Functional characterization of OXTR-associated enhancers.

The oxytocin receptor (OXTR) has a vital role in regulating human behavior, controlling lactation, parturition, pair bonding, maternal behavior, anxiety, and sociability. However, its regulatory elements and how variation in these sequences lead to behavioral changes remain largely unknown. Here, we identified seven OXTR candidate cis-regulatory elements (cCREs) from mouse and human hypothalamus single-cell RNA/ATAC-seq data and characterized them in cells and mice. Luciferase assays in hypothalamus cell lines identified three of the seven to be functional enhancers. Mouse enhancer assays for the most robust enhancer, OXTR candidate enhancer 7 (OCE7), found it to be active in the mouse olfactory bulb at postnatal day 28 and day 56. In summary, using genomic data coupled with cell and mouse enhancer assays, we characterized the OXTR regulatory landscape and identified a novel olfactory bulb OXTR-associated enhancer.