Constância M, Pickard B, Kelsey G, Reik W
Programme in Developmental Genetics, The Babraham Institute, Cambridge CB2 4AT, UK.
Genome Res. 1998 Sep;8(9):881-900. doi: 10.1101/gr.8.9.881.
A number of recent studies have provided new insights into mechanisms that regulate genomic imprinting in the mammalian genome. Regions of allele-specific differential methylation (DMRs) are present in all imprinted genes examined. Differential methylation is erased in germ cells at an early stage of their development, and germ-line-specific methylation imprints in DMRs are reestablished around the time of birth. After fertilization, differential methylation is retained in core DMRs despite genome-wide demethylation and de novo methylation during preimplantation and early postimplantation stages. Direct repeats near CG-rich DMRs may be involved in the establishment and maintenance of allele-specific methylation patterns. Imprinted genes tend to be clustered; one important component of clustering is enhancer competition, whereby promoters of linked imprinted genes compete for access to enhancers. Regional organization and spreading of the epigenotype during development is also important and depends on DMRs and imprinting centers. The mechanism of cis spreading of DNA methylation is not known, but precedent is provided by the Xist RNA, which results in X chromosome inactivation in cis. Reading of the somatic imprints could be carried out by transcription factors that are sensitive to methylation, or by methyl-cytosine-binding proteins that are involved in transcriptional repression through chromatin remodeling.
最近的一些研究为调控哺乳动物基因组中印迹基因的机制提供了新的见解。在所有已检测的印迹基因中均存在等位基因特异性差异甲基化区域（DMRs）。差异甲基化在生殖细胞发育的早期阶段被消除，而DMRs中的生殖系特异性甲基化印记在出生前后重新建立。受精后，尽管在植入前和植入后早期阶段全基因组会发生去甲基化和从头甲基化，但核心DMRs中的差异甲基化仍会保留。富含CG的DMRs附近的直接重复序列可能参与等位基因特异性甲基化模式的建立和维持。印迹基因倾向于成簇；成簇的一个重要组成部分是增强子竞争，即连锁印迹基因的启动子竞争获取增强子的机会。发育过程中表观基因型的区域组织和扩展也很重要，并且依赖于DMRs和印记中心。DNA甲基化顺式扩展的机制尚不清楚，但Xist RNA提供了先例，它导致X染色体顺式失活。体细胞印记的读取可以由对甲基化敏感的转录因子进行，或者由通过染色质重塑参与转录抑制的甲基胞嘧啶结合蛋白进行。
