DNA METHYLATION AND EPIGENETIC MECHANISMS
DNA METHYLATION AND EPIGENETIC MECHANISMS
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DOI：
10.1007/bf02991575
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发表时间：
1989-08-01
期刊：
影响因子：
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通讯作者：
HOLLIDAY, R
中科院分区：
文献类型：
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作者：
HOLLIDAY, R
基因对于遗传信息的代代传递至关重要，而且这种遗传机制已被充分理解。基因对于展开发育的遗传程序也是必不可少的，但管理这一过程的规则是模糊的。表观遗传学包括研究发育过程中基因的开启和关闭，体细胞分裂后基因活性的分离，以及特定细胞中特定基因活性谱的稳定遗传。其中一些过程可以用DNA修饰来解释，特别是DNA甲基化模式的变化和该模式的遗传性。有强有力的证据表明，DNA甲基化在培养的哺乳动物细胞中的基因活性的控制中起着重要的作用，并描述了在DNA甲基化中受影响的CHO突变株的性质。人二倍体细胞在连续传代培养过程中逐渐失去胞嘧啶甲基化，这可能与其体外衰老有关。也有证据表明，DNA修饰可以通过种系遗传。经典遗传学基于对DNA碱基序列中所有类型变化的研究，但通过表观遗传机制控制基因活性的规则必然不同。它们的阐明将取决于发展的理论框架和在分子、染色体和细胞水平上的实验研究。
Genes are essential for the transmission of genetic information from generation to generation, and this mechanism of inheritance is fully understood. Genes are also essential for unfolding the genetic program for development, but the rules governing this process are obscure. Epigenetics comprises the study of the switching on and off of genes during development, the segregation of gene activities following somatic cell division, and the stable inheritance of a given spectrum of gene activities in specific cells. Some of these processes may be explained by DNA modification, particularly changes in the pattern of DNA methylation and the heritability of that pattern. There is strong evidence that DNA methylation plays an important role in the control of gene activity in cultured mammalian cells, and the properties of a CHO mutant strain affected in DNA methylation are described. Human diploid cells progressively lose cytosine methylation during serial subculture, and this may be related to their in vitro senescence. There is also evidence that DNA modifications can be inherited through the germ line. Classical genetics is based on the study of all types of change in DNA base sequence, but the rules governing the activity of genes by epigenetic mechanisms are necessarily different. Their elucidation will depend both on a theoretical framework for development and on experimental studies at the molecular, chromosomal, and cellular levels.