Exp Mol Med.
2007 Feb;39(1):84-96.
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
- Affiliations
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- 1Department of Biochemistry and Molecular Biology, College of Pharmacy, Sungkyunkwan University, Suwon 440-746, Korea. jhhan551@skku.edu
- 2MGen, Inc., World Meridian Venture Center, #60-24, Gasan-dong, Guemchun-gu, Seoul 153-781, Korea.
- 3Ilchun Molecular Medicine Institute, Medical Research Center, Seoul National University College of Medicine, Seoul 110-799, Korea.
- 4Department of Pharmacology, College of Medicine, Kwandong University, Gangneung 210-701, Korea.
- 5Macrogen, Inc., World Meridian Venture Center 10F, #60-24, Gasan-dong, Guemchun-gu, Seoul 153-781, Korea.
- 6Division of Animal Science and Resources, Research Center for Transgenic Cloned Pigs, Chungnam National University, Daejeon 305-764, Korea.
Abstract
- 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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