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表观遗传学:细胞中组织依赖性及差异甲基化区域的DNA甲基化图谱。

Epigenetics: the DNA methylation profile of tissue-dependent and differentially methylated regions in cells.

作者信息

Ohgane J, Yagi S, Shiota K

机构信息

Laboratory of Cellular Biochemistry, Animal Resource Sciences/Veterinary Medical Sciences, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.

出版信息

Placenta. 2008 Mar;29 Suppl A:S29-35. doi: 10.1016/j.placenta.2007.09.011. Epub 2007 Nov 26.

Abstract

Methylation of DNA, which occurs at cytosines of CpG sequences, is a unique chemical modification of the vertebrate genome. Methylation patterns can be copied to daughter DNA after mitosis; thus DNA methylation has been suggested to act as a "cellular memory of the genome function". Genome-wide analysis of DNA methylation revealed that there are numerous tissue-dependent differentially methylated regions (T-DMRs) in unique sequences of the mammalian genome. There are T-DMRs in both CpG-rich and -poor sequences. Methylation of T-DMRs is responsible for gene-silencing and chromatin structure change. Each tissue/cell type has a unique DNA methylation profile that consists of methylation patterns of numerous loci in the genome. DNA methylation profiles are not associated with bulk DNA, which is mainly comprised of repetitive sequences. Disruption of DNA methylation profiles putatively produce abnormal cells and tissues. Cloned mice produced by somatic nuclear transfer are associated with aberrant DNA methylation profiles. Tissue/cell type-specific DNA methylation profiles can provide a novel viewpoint for understanding normal and aberrant development, in terms of both differentiation and reproduction.

摘要

DNA甲基化发生在CpG序列的胞嘧啶上,是脊椎动物基因组独特的化学修饰。甲基化模式在有丝分裂后可复制到子代DNA;因此,有人提出DNA甲基化可作为“基因组功能的细胞记忆”。全基因组DNA甲基化分析表明,在哺乳动物基因组的独特序列中存在大量组织依赖性差异甲基化区域(T-DMR)。富含CpG和缺乏CpG的序列中均存在T-DMR。T-DMR的甲基化导致基因沉默和染色质结构改变。每种组织/细胞类型都有独特的DNA甲基化图谱,该图谱由基因组中众多位点的甲基化模式组成。DNA甲基化图谱与主要由重复序列组成的大量DNA无关。DNA甲基化图谱的破坏可能产生异常细胞和组织。通过体细胞核移植产生的克隆小鼠与异常的DNA甲基化图谱有关。组织/细胞类型特异性的DNA甲基化图谱可以为从分化和繁殖方面理解正常和异常发育提供一个新的视角。

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