title: Coordinated change of a ratio of methylated H3-lysine 4 or acetylated H3 to acetylated H4 and DNA methylation is associated with tissue-specific gene expression in cloned pig.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Pharmacy, Sungkyunkwan University, Suwon 440-746, Korea.
authors.forename: Jae-Ku
authors.initials: JK
authors.lastname: Kang
authors.forename: Kwang-Wook
authors.initials: KW
authors.lastname: Park
authors.forename: Yeon-Gu
authors.initials: YG
authors.lastname: Chung
authors.forename: Jueng-Soo
authors.initials: JS
authors.lastname: You
authors.forename: Yong-Kee
authors.initials: YK
authors.lastname: Kim
authors.forename: Seung-Hyeon
authors.initials: SH
authors.lastname: Lee
authors.forename: Seung-Pyo
authors.initials: SP
authors.lastname: Hong
authors.forename: Ki-Myung
authors.initials: KM
authors.lastname: Choi
authors.forename: Ki-Nam
authors.initials: KN
authors.lastname: Heo
authors.forename: Jae-Goo
authors.initials: JG
authors.lastname: Seol
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Dong-Il
authors.initials: DI
authors.lastname: Jin
authors.forename: Chang-Sik
authors.initials: CS
authors.lastname: Park
authors.forename: Jeong-Sun
authors.initials: JS
authors.lastname: Seo
authors.forename: Hyang-Woo
authors.initials: HW
authors.lastname: Lee
authors.forename: Jeung-Whan
authors.initials: JW
authors.lastname: Han
mesh_terms: D000107:Acetylation; D000818:Animals; D030801:Animals, Genetically Modified; D002478:Cells, Cultured; D019175:DNA Methylation; D004423:Ear; D005347:Fibroblasts; D015870:Gene Expression; D020868:Gene Silencing; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D009928:Organ Specificity / Q000235:genetics; D013552:Swine; D019076:Transgenes / Q000235:genetics*
chemical_list: D006657:Histones; D006655:Histone Deacetylases; D008239:Lysine