Michael Kelly1, Gaurang Daftary, Hugh S Taylor. 1. Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA.
Abstract
OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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.
OBJECTIVE: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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: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.
Authors: Q F Wang; Y J Li; J F Dong; B Li; J J Kaberlein; L Zhang; F E Arimura; R T Luo; J Ni; F He; J Wu; R Mattison; J Zhou; C Z Wang; S Prabhakar; M A Nobrega; M J Thirman Journal: Leukemia Date: 2013-09-11 Impact factor: 11.528