An autoregulatory element maintains HOXA10 expression in endometrial epithelial cells.
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.


METHODS
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.


CONCLUSIONS
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.
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA.
Michael
M
Kelly
Gaurang
G
Daftary
Hugh S
HS
Taylor
D002478:Cells, Cultured; D004717:Endometrium / Q000166:cytology*; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D006706:Homeostasis; D006801:Humans
D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; C069634:HOXA10 protein, human