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Regulation of the activity of the transcription factor Runx2 by two homeobox proteins, Msx2 and Dlx5
Author(s) -
Shirakabe Kyoko,
Terasawa Kazuya,
Miyama Katsuyoshi,
Shibuya Hiroshi,
Nishida Eisuke
Publication year - 2001
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1046/j.1365-2443.2001.00466.x
Subject(s) - dlx5 , runx2 , biology , hnf1b , emx2 , homeobox , transcription factor , homeobox protein nkx 2.5 , homeobox a1 , cdx2 , repressor , transcription (linguistics) , microbiology and biotechnology , genetics , gene , linguistics , philosophy
Background Runx2, formerly called PEBP2αA or Cbfa1, is a transcription factor whose deletion causes a complete lack of ossification. It directly regulates the expression of osteoblast‐specific genes through the osteoblast‐specific cis ‐acting element found in the promoter region of these genes. Results In this study, we have found conditions in which induction of the expression of Runx2 is not accompanied by expression of an osteoblast‐specific gene, osteocalcin in C2C12 cells. This finding suggests the existence of a repressor of the activity of Runx2. We have then found that the homeobox protein Msx2 is able to repress the transcription activity of Runx2 by interacting with it. Furthermore, our results have shown that the other homeobox protein Dlx5 has an activity which interferes with both abilities of Msx2 to interact with Runx2 and repress its transcription activity. It has previously been shown that a missense mutation of Msx2 (P148H) causes Boston‐type craniosynostosis in humans. Interestingly, while this mutant form of Msx2 was able to bind to Runx2 and repress its activity, these abilities of Msx2 (P148H) were not subject to regulation by Dlx5. Conclusion These results suggest that regulation of the activity of Runx2 by Msx2 and Dlx5 plays an important role in the mammalian skull development .