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Direct Regulation of HOXA10 by 1,25-(OH)₂D₃ in Human Myelomonocytic Cells and Human Endometrial Stromal Cells

Yale University School of Medicine, New Haven, Connecticut 06520-8063

Address all correspondence and requests for reprints to: Hugh S. Taylor, Division of Reproductive Endocrinology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520-8063. E-mail: hugh.taylor{at}yale.edu.

Vitamin D receptor (VDR) and the functionally active form of its ligand, 1,25-(OH)₂D₃, have been implicated in female reproduction function and myeloid leukemic cell differentiation. HOXA10 is necessary for embryo implantation and fertility, as well as hematopoeitic development. In this study, we identified a direct role of vitamin D in the regulation of HOXA10 in primary human endometrial stromal cells, the human endometrial stromal cell line (HESC), and in the human myelomonocytic cell line, U937. Treatment of primary endometrial stromal cells, or the cell lines HESC and U937 with 1,25-(OH)₂D₃ increased HOXA10 mRNA and protein expression. VDR mRNA and protein were detected in primary uterine stromal cells as well as HESC and U937 cells. We cloned the HOXA10 upstream regulatory sequence and two putative vitamin D response elements (VDRE) into luciferase reporter constructs and transfected primary stromal cells and HESC. One putative VDRE (P1: –385 to –434 bp upstream of HOXA10) drove reporter gene expression in response to treatment with 1,25-(OH)₂D₃. In EMSA, VDR demonstrated binding to the HOXA10 VDRE in the presence of 1,25-(OH)₂D₃. 1,25-(OH)₂D₃ up-regulates HOXA10 expression by binding VDR and interacting with a VDRE in the HOXA10 regulatory region. Direct regulation of HOXA10 by vitamin D has implications for fertility and myeloid differentiation.

NURSA Molecule Pages Link:

Nuclear Receptors:   VDR

Ligands:   Calcitriol

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