Verona Raluca I, Mann Mellissa R W, Bartolomei Marisa S
Howard Hughes Medical Institute and Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148, USA.
Annu Rev Cell Dev Biol. 2003;19:237-59. doi: 10.1146/annurev.cellbio.19.111401.092717.
An intriguing characteristic of imprinted genes is that they often cluster in large chromosomal domains, raising the possibility that gene-specific and domain-specific mechanisms regulate imprinting. Several common features emerged from comparative analysis of four imprinted domains in mice and humans: (a) Certain genes appear to be imprinted by secondary events, possibly indicating a lack of gene-specific imprinting marks; (b) some genes appear to resist silencing, predicting the presence of cis-elements that oppose domain-specific imprinting control; (c) the nature of the imprinting mark remains incompletely understood. In addition, common silencing mechanisms are employed by the various imprinting domains, including silencer elements that nucleate and propagate a silent chromatin state, insulator elements that prevent promoter-enhancer interactions when hypomethylated on one parental allele, and antisense RNAs that function in silencing the overlapping sense gene and more distantly located genes. These commonalities are reminiscent of the behavior of genes subjected to, and the mechanisms employed in, dosage compensation.
印记基因的一个有趣特征是它们常常在大的染色体区域中聚集，这增加了基因特异性和区域特异性机制调控印记的可能性。对小鼠和人类四个印记区域的比较分析得出了几个共同特征：（a）某些基因似乎是由次级事件印记的，这可能表明缺乏基因特异性的印记标记；（b）一些基因似乎抵抗沉默，预示着存在反对区域特异性印记控制的顺式元件；（c）印记标记的性质仍未完全了解。此外，各种印记区域采用了共同的沉默机制，包括成核并传播沉默染色质状态的沉默子元件、当一个亲本等位基因发生低甲基化时阻止启动子 - 增强子相互作用的绝缘子元件，以及在沉默重叠的正义基因和更远距离的基因中起作用的反义RNA。这些共性让人联想到经历剂量补偿的基因的行为以及所采用的机制。
