Regulation of the activity of the transcription factor Runx2 by two homeobox proteins, Msx2 and Dlx5

Kyoko Shirakabe, Kazuya Terasawa, Katsuyoshi Miyama, Hiroshi Shibuya, Eisuke Nishida

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

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 D1x5 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.

Original languageEnglish
Pages (from-to)851-856
Number of pages6
JournalGenes to Cells
Volume6
Issue number10
DOIs
Publication statusPublished - 2001

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Homeodomain Proteins
Osteoblasts
Transcription Factors
Genes
Osteocalcin
Missense Mutation
Genetic Promoter Regions
Osteogenesis
Skull

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Regulation of the activity of the transcription factor Runx2 by two homeobox proteins, Msx2 and Dlx5. / Shirakabe, Kyoko; Terasawa, Kazuya; Miyama, Katsuyoshi; Shibuya, Hiroshi; Nishida, Eisuke.

In: Genes to Cells, Vol. 6, No. 10, 2001, p. 851-856.

Research output: Contribution to journalArticle

Shirakabe, Kyoko ; Terasawa, Kazuya ; Miyama, Katsuyoshi ; Shibuya, Hiroshi ; Nishida, Eisuke. / Regulation of the activity of the transcription factor Runx2 by two homeobox proteins, Msx2 and Dlx5. In: Genes to Cells. 2001 ; Vol. 6, No. 10. pp. 851-856.
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