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Methylation of the Mouse Dlx5 and Osx Gene Promoters Regulates Cell Type-specific Gene Expression  

Lee, Ji Yun (Department of Anatomy, School of Medicine, Kyungpook National University)
Lee, Yu Mi (Department of Anatomy, School of Medicine, Kyungpook National University)
Kim, Mi Jin (Department of Anatomy, School of Medicine, Kyungpook National University)
Choi, Je Yong (Skeletal Diseases Genome Research Center, Kyungpook National University Hospital)
Park, Eui Kyun (Skeletal Diseases Genome Research Center, Kyungpook National University Hospital)
Kim, Shin Yoon (Skeletal Diseases Genome Research Center, Kyungpook National University Hospital)
Lee, Sam Poong (Department of Genetic Engineering, Daegu University)
Yang, Jae Sup (Department of Genetic Engineering, Daegu University)
Kim, Dong Sun (Department of Anatomy, School of Medicine, Kyungpook National University)
Publication Information
Molecules and Cells / v.22, no.2, 2006 , pp. 182-188 More about this Journal
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 methylationspecific 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 timedependent 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.
Keywords
5-Aza-2-Deoxycytidine; Cell Type-specific Expression; DNA Methylation; Dlx5; Methylation-specific PCR; Osx;
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