Malcore Rebecca M, Kalantry Sundeep
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48105, USA.
Epigenomes. 2024 Feb 10;8(1):8. doi: 10.3390/epigenomes8010008.
The mammalian sexes are distinguished by the X and Y chromosomes. Whereas males harbor one X and one Y chromosome, females harbor two X chromosomes. To equalize X-linked gene expression between the sexes, therian mammals have evolved X-chromosome inactivation as a dosage compensation mechanism. During X-inactivation, most genes on one of the two X chromosomes in females are transcriptionally silenced, thus equalizing X-linked gene expression between the sexes. Two forms of X-inactivation characterize eutherian mammals, imprinted and random. Imprinted X-inactivation is defined by the exclusive inactivation of the paternal X chromosome in all cells, whereas random X-inactivation results in the silencing of genes on either the paternal or maternal X chromosome in individual cells. Both forms of X-inactivation have been studied intensively in the mouse model system, which undergoes both imprinted and random X-inactivation early in embryonic development. Stable imprinted and random X-inactivation requires the induction of the Xist long non-coding RNA. Following its induction, Xist RNA recruits proteins and complexes that silence genes on the inactive-X. In this review, we present a current understanding of the mechanisms of Xist RNA induction, and, separately, the establishment and maintenance of gene silencing on the inactive-X by Xist RNA during imprinted and random X-inactivation.
哺乳动物的性别由X和Y染色体决定。雄性有一条X染色体和一条Y染色体，而雌性有两条X染色体。为了使两性之间X连锁基因的表达达到平衡，有胎盘哺乳动物进化出了X染色体失活作为一种剂量补偿机制。在X染色体失活过程中，雌性两条X染色体中的一条上的大多数基因会被转录沉默，从而使两性之间X连锁基因的表达达到平衡。真兽亚纲哺乳动物的X染色体失活有两种形式，即印记失活和随机失活。印记X染色体失活的定义是，在所有细胞中父本X染色体被特异性失活，而随机X染色体失活则导致单个细胞中父本或母本X染色体上的基因沉默。在小鼠模型系统中对这两种形式的X染色体失活都进行了深入研究，小鼠在胚胎发育早期会经历印记X染色体失活和随机X染色体失活。稳定的印记X染色体失活和随机X染色体失活需要诱导Xist长链非编码RNA。Xist RNA被诱导后，会招募使失活X染色体上的基因沉默的蛋白质和复合物。在这篇综述中，我们阐述了目前对Xist RNA诱导机制的理解，以及在印记X染色体失活和随机X染色体失活过程中，Xist RNA在失活X染色体上建立和维持基因沉默的机制。
