S-Space College of Dentistry/School of Dentistry (치과대학/치의학대학원) Dept. of Dentistry (치의학과) Journal Papers (저널논문_치의학과)
Dlx5 specifically regulates Runx2 type II expression by binding to homeodomain-response elements in the Runx2 distal promoter
- Lee, Mi-Hye; Kim, Youn-Jeong; Yoon, Won-Joon; Kim, Jee-In; Kim, Byung-Gyu; Hwang, Yoo-Seok; Wozney, John M.; Chi, Xin-Zi; Bae, Suk-Chul; Choi, Kang-Young; Cho, Je-Yoel; Choi, Je-Yong; Ryoo, Hyun-Mo
- Issue Date
- THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 280, NO. 42, pp. 35579–35587.
- Two major isoforms of the Runx2 gene are expressed by alternative
promoter usage: Runx2 type I (Runx2-I) is derived from the
proximal promoter (P2), and Runx2 type II (Runx2-II) is produced
by the distal promoter (P1). Our previous results indicate that Dlx5
mediates BMP-2-induced Runx2 expression and osteoblast differentiation
(Lee, M.-H., Kim, Y-J., Kim, H-J., Park, H-D., Kang, A-R.,
Kyung, H.-M., Sung, J-H., Wozney, J. M., Kim, H-J., and Ryoo, H-M.
(2003) J. Biol. Chem. 278, 34387–34394). However, little is known of
the molecular mechanisms by which Dlx5 up-regulates Runx2
expression in BMP-2 signaling. Here, Runx2-II expression was
found to be specifically stimulated by BMP-2 treatment or by Dlx5
overexpression. In addition, BMP-2, Dlx5, and Runx2-II were found
to be expressed in osteogenic fronts and parietal bones of the developing
cranial vault and Runx2-I and Msx2 in the sutural mesenchyme.
Furthermore, Runx2 P1 promoter activity was strongly
stimulated by Dlx5 overexpression, whereas Runx2 P2 promoter
activity was not. Runx2 P1 promoter deletion analysis indicated that
the Dlx5-specific response is due to sequences between 756 and
342 bp of the P1 promoter, where three Dlx5-response elements
are located. Dlx5 responsiveness to these elements was confirmed
by gel mobility shift assay and site-directed mutagenesis. Moreover,
Msx2 specifically suppressed the Runx2 P1 promoter, and the
responsible region overlaps with that recognized by Dlx5. In summary,
Dlx5 specifically transactivates the Runx2 P1 promoter, and
its action on the P1 promoter is antagonized by Msx2.
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