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KMID : 0620920070390010084
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Experimental & Molecular Medicine
2007 Volume.39 No. 1 p.84 ~ p.96
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Coordinated change of a ratio of methylated H3-Iysine 4 or acetylated H3 to acetylated H4 and DNA methylation is associated with tissue-specific gene expression in cloned pig
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Kang Jae-Ku
Park Kwang-Wook
Chung Yeon-Gu
You Jueng-Soo
Lee Seung-Hyeon
Hong Seung-Pyo
Choi Ki-Myung
Heo Ki-Nam
Seol Jae-Goo
Lee Hyang-Woo
Han Jeung-Whan
Kim Yong-Kee
Lee Jong-Ho
Jin Dong-Il
Park Chang-Sik
Seo Jeong-Sun
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Abstract
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Various cell types in higher multicellular organisms are genetically homogenous, but are functionally and morphologically heterogeneous due to the differential expression of genes during development, which appears to be controlled by epigenetic mechanisms. However, the exact molecular mechanisms that govern the tissue-specific gene expression are poorly understood. Here, we show that dynamic changes in histone modifications and DNA methylation in the upstream coding region of a gene containing the transcription initiation site determine the tissue-specific gene expression pattern. The tissue-specific expression of the transgene correlated with DNA demethylation at specific CpG sites as well as significant changes in histone modifications from a low ratio of methylated H3- lysine 4 or acetylated H3-lysine 9, 14 to acetylated H4 to higher ratios. Based on the programmed status of transgene silenced in cloned mammalian ear- derived fibroblasts, the transgene could be reprogrammed by change of histone modification and DNA methylation by inhibiting both histone deacetylase and DNA methylation, resulting in high expression of the transgene. These findings indicate that dynamic change of histone modification and DNA methylation is potentially important in the establishment and maintenance of tissue-specific gene expression.
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KEYWORD
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DNA methylation, DNA modification methylases, gene expression, open reading frames, organ specificity
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