Methylation of the mouse Dlx5 and Osx gene promoters regulates cell type-specific gene expression

Ji Yun Lee, Yu Mi Lee, Mi Jin Kim, Je Yong Choi, Eui Kyun Park, Shin Yoon Kim, Sam Poong Lee, Jae Sup Yang, Dong Sun Kim

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

Dlx5 and Osx are master regulatory proteins essential for initiating the cascade leading to osteoblast differentiation in mammals, but the mechanism of osteoblast-specific expression is not fully understood. DNA methylation at CpG sequences is involved in tissue and cell type-specific gene expression. We investigated the methylation status of Dlx5 and Osx in osteogenic and nonosteogenic cell lines by methylation-specific PCR (MSP). The CpG dinucleotides of the Dlx5 and Osx promoter regions were unmethylated in osteogenic cell lines transcribing these genes but methylated in nonosteogenic cell lines. Treatment of C2C12 cells with 5-AzadC induced dose- and time-dependent expression of Dlx5 and Osx mRNA by demethylating the corresponding promoters. Furthermore the mRNAs for the osteoblast markers ALP and OC, which were undetectable in untreated cells, gradually increased after 5-AzadC treatment. In addition, BMP-2 stimulation induced Dlx5 expression by hypomethylating its promoter. These findings suggest that DNA methylation plays an important role in cell type-specific expression of Dlx5 and OSX.

Original languageEnglish
Pages (from-to)182-188
Number of pages7
JournalMolecules and Cells
Volume22
Issue number2
StatePublished - Oct 2006

Keywords

  • 5-Aza-2-deoxycytidine
  • Cell type-specific expression
  • Dlx5
  • DNA methylation
  • Methylation-specific PCR
  • Osx

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