Integrated chromatin immunoprecipitation sequencing and microarray analysis identifies FOXA2 target genes in the glands of the mouse uterus

Uterine glands and their secretions are indispensable for endometrial function and fertility; however, the mechanisms regulating their development and function are not well understood. Forkhead transcription factor box A2 (FOXA2) is uniquely expressed in the glandular epithelial (GE) cells of the uterus, and conditional deletion of Foxa2 after birth impedes uterine gland development. An integrative approach was used here to define the FOXA2 cistrome in the murine uterus. Genome-wide mapping of FOXA2 binding sites was combined with transcriptomic analyses of isolated GE and Foxa2-deleted uteri. ChIP-Seq analyses found the number of FOXA2 target genes was substantially greater in the adult (8893) than neonatal uterus (1101). In the neonatal uterus, FOXA2-bound and GE-expressed genes (469) were enriched for developmentally related processes, including cell cycle, cell junction, focal adhesion, and WNT signaling. In the adult uterus, FOXA2-bound and GE-expressed genes (3730) were enriched for functional processes, including metabolic pathways, focal adhesion, bacterial invasion of epithelial cells, and WNT signaling. Analysis of the uterine FOXA2 cistrome provides novel insights into mechanisms governing endometrial gland development and function, which are important to understand fundamental aspects of uterine differentiation, regeneration and disease.