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.
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.
Kang
Jae-Ku
JK
Department of Biochemistry and Molecular Biology, College of Pharmacy, Sungkyunkwan University, Suwon 440-746, Korea.
Park
Kwang-Wook
KW
Chung
Yeon-Gu
YG
You
Jueng-Soo
JS
Kim
Yong-Kee
YK
Lee
Seung-Hyeon
SH
Hong
Seung-Pyo
SP
Choi
Ki-Myung
KM
Heo
Ki-Nam
KN
Seol
Jae-Goo
JG
Lee
Jong-Ho
JH
Jin
Dong-Il
DI
Park
Chang-Sik
CS
Seo
Jeong-Sun
JS
Lee
Hyang-Woo
HW
Han
Jeung-Whan
JW
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*
D006657:Histones; D006655:Histone Deacetylases; D008239:Lysine