Howard Hughes Medical Institute, Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Cell. 2013 Mar 14;152(6):1308-23. doi: 10.1016/j.cell.2013.02.016.
X chromosome inactivation and genomic imprinting are classic epigenetic processes that cause disease when not appropriately regulated in mammals. Whereas X chromosome inactivation evolved to solve the problem of gene dosage, the purpose of genomic imprinting remains controversial. Nevertheless, the two phenomena are united by allelic control of large gene clusters, such that only one copy of a gene is expressed in every cell. Allelic regulation poses significant challenges because it requires coordinated long-range control in cis and stable propagation over time. Long noncoding RNAs have emerged as a common theme, and their contributions to diseases of imprinting and the X chromosome have become apparent. Here, we review recent advances in basic biology, the connections to disease, and preview potential therapeutic strategies for future development.
X 染色体失活和基因组印迹是经典的表观遗传过程，在哺乳动物中，如果调控不当，会导致疾病。虽然 X 染色体失活是为了解决基因剂量问题而进化的，但基因组印迹的目的仍然存在争议。然而，这两种现象通过等位基因控制的大型基因簇而统一起来，使得每个细胞中只表达一个基因的一个副本。等位基因调控带来了巨大的挑战，因为它需要在顺式中进行协调的长距离调控，并随着时间的推移保持稳定的传播。长非编码 RNA 已成为一个共同的主题，它们对印迹和 X 染色体疾病的贡献已经变得明显。在这里，我们回顾了基础生物学的最新进展、与疾病的联系，并预览了未来发展的潜在治疗策略。
