An autoregulatory element maintains HOXA10 expression in endometrial epithelial cells.

Abstract

HOXA10 is necessary for endometrial receptivity and regulated by sex steroids. Secretory phase HOXA10 expression increases in endometrial epithelial cells, despite the loss of progesterone receptor. Stromal-epithelial molecular communication likely transmits progesterone signaling from progesterone receptor containing stromal cells to epithelium. Here we investigated an alternative hypothesis, persistent HOXA10 expression by autoregulation. Nested segments of the HOXA10 5' regulatory region were cloned into a pGL3-Luciferase reporter construct and tested for HOXA10-induced reporter activity. Direct binding was assayed by electrophoretic mobility shift assay. One 370 base pair element drove reporter gene expression specifically in response to HOXA10 in Ishikawa cells but not in BT-20 cells. This element contained a site that bound HOXA10 protein. HOXA10 expression is driven by an autoregulatory element in the 5' regulatory region of the gene. Autoregulation is a novel alternative molecular mechanism by which steroid-induced gene expression can be maintained in the absence of steroid receptors.