Holliday R
CSIRO Laboratory for Molecular Biology, North Ryde, New South Wales, Australia.
Philos Trans R Soc Lond B Biol Sci. 1990 Jan 30;326(1235):329-38. doi: 10.1098/rstb.1990.0015.
Classical genetics has revealed the mechanisms for the transmission of genes from generation to generation, but the strategy of the genes in unfolding the developmental programme remains obscure. Epigenetics comprises the study of the mechanisms that impart temporal and spatial control on the activities of all those genes required for the development of a complex organism from the zygote to the adult. Epigenetic changes in gene activity can be studied in relation to DNA methylation in cultured mammalian cells and it is also possible to isolate and characterize mutants with altered DNA methylase activity. Although this experimental system is quite far removed from the epigenetic controls acting during development it does provide the means to clarify the rules governing the silencing of genes by specific DNA methylation and their reactivation by demethylation. This in turn will facilitate studies on the control of gene expression in somatic cells of the developing organism or the adult. The general principles of epigenetic mechanisms can be defined. There are extreme contrasts between instability or switches in gene expression, such as those in stem-line cells, and the stable heritability of a specialized pattern of gene activities. In some situations cell lineages are known to be important, whereas in others coordinated changes in groups of cells have been demonstrated. Control of numbers of cell divisions and the size of organisms, or parts of organisms, is also essential. The epigenetic determination of gene expression can be reversed or reprogrammed in the germ line. The extent to which methylation or demethylation of specific DNA sequences can help explain these basic epigenetic mechanisms is briefly reviewed.
经典遗传学已经揭示了基因代代相传的机制，但是基因在展开发育程序中的策略仍然不明。表观遗传学包括对所有那些从受精卵发育为成体复杂生物体所需基因的活动施加时空控制机制的研究。基因活性的表观遗传变化可以在培养的哺乳动物细胞中结合DNA甲基化来研究，并且也有可能分离和鉴定具有改变的DNA甲基化酶活性的突变体。尽管这个实验系统与发育过程中起作用的表观遗传控制相去甚远，但它确实提供了阐明特定DNA甲基化使基因沉默以及去甲基化使其重新激活的规则的手段。这反过来将促进对发育中的生物体或成体体细胞中基因表达控制的研究。表观遗传机制的一般原则可以被定义。基因表达的不稳定性或转换，如在干细胞系中的那些，与基因活动特定模式的稳定遗传性之间存在极端差异。在某些情况下，细胞谱系已知是重要的，而在其他情况下，已证明细胞群中的协调变化。控制细胞分裂数量以及生物体或生物体部分的大小也至关重要。基因表达的表观遗传决定在种系中可以被逆转或重新编程。本文简要综述了特定DNA序列的甲基化或去甲基化在多大程度上有助于解释这些基本的表观遗传机制。
