Reik Wolf
Laboratory of Developmental Genetics and Imprinting, The Babraham Institute, Cambridge CB22 3AT, UK.
Nature. 2007 May 24;447(7143):425-32. doi: 10.1038/nature05918.
During development, cells start in a pluripotent state, from which they can differentiate into many cell types, and progressively develop a narrower potential. Their gene-expression programmes become more defined, restricted and, potentially, 'locked in'. Pluripotent stem cells express genes that encode a set of core transcription factors, while genes that are required later in development are repressed by histone marks, which confer short-term, and therefore flexible, epigenetic silencing. By contrast, the methylation of DNA confers long-term epigenetic silencing of particular sequences--transposons, imprinted genes and pluripotency-associated genes--in somatic cells. Long-term silencing can be reprogrammed by demethylation of DNA, and this process might involve DNA repair. It is not known whether any of the epigenetic marks has a primary role in determining cell and lineage commitment during development.
在发育过程中，细胞起始于多能状态，在此状态下它们能够分化为多种细胞类型，然后逐渐具有更窄的分化潜能。它们的基因表达程序变得更加明确、受限，并且可能被“锁定”。多能干细胞表达编码一组核心转录因子的基因，而发育后期所需的基因则被组蛋白标记抑制，这些组蛋白标记赋予短期的、因而也是灵活的表观遗传沉默。相比之下，DNA甲基化赋予体细胞中特定序列（转座子、印记基因和多能性相关基因）长期的表观遗传沉默。长期沉默可以通过DNA去甲基化重新编程，这个过程可能涉及DNA修复。目前尚不清楚在发育过程中是否有任何表观遗传标记在决定细胞和谱系定向方面起主要作用。
