GSE100023
ERa DNA Binding Profiles of IGF1 and ICI182,780 treated mouse uterus from manuscript: Role of ERa in Mediating Female Uterine Transcriptional Responses to IGF1
Estrogen (E2) signaling through its nuclear receptor, estrogen receptor a (ERa) increases insulin-like growth factor 1 (IGF1) in the rodent uterus, which then initiates further signals via the IGF1 receptor (IGF1R). Directly administering IGF1 results in similar biological and transcriptional uterine responses. Our studies using global ERa-null mice demonstrated a loss of uterine biological responses of the uterus to E2 or IGF1 treatment, while maintaining transcriptional responses to IGF1. To address this discrepancy in the need for uterine ERa in mediating the IGF1 transcriptional vs. growth responses, we assessed the IGF1 transcriptional responses in PgrCre+Esr1f/f (called ERaUtcKO) mice, which selectively lack ERa in progesterone receptor (PGR) expressing cells, including all uterine cells, while maintaining ERa expression in other tissues and cells that do not express Pgr. Additionally, we profiled IGF1-induced ERa binding sites in uterine chromatin using ChIP-seq. Herein, we explore the transcriptional and molecular signaling that underlies our findings to refine our understanding of uterine IGF1 signaling and identify ERa-mediated and ERa-independent uterine transcriptional responses. Defining these mechanisms in vivo in whole tissue and animal contexts provides details of nuclear receptor mediated mechanisms that impact biological systems and have potential applicability to reproductive processes of humans, livestock and wildlife. Overall design: ERa Chip seq of IGF1 or ICI182,780 treated mouse usterine tissue, pools of 5 uteri/sample