Abstract
A striking difference between male and female nuclei was recognized early on by the presence of a condensed chromatin body only in female cells. Mary Lyon proposed that X inactivation or silencing of one X chromosome at random in females caused this structural difference. Subsequent studies have shown that the inactive X chromosome (Xi) does indeed have a very distinctive structure compared to its active counterpart and all autosomes in female mammals. In this review, we will recap the discovery of this fascinating biological phenomenon and seminal studies in the field. We will summarize imaging studies using traditional microscopy and super-resolution technology, which revealed uneven compaction of the Xi. We will then discuss recent findings based on high-throughput sequencing techniques, which uncovered the distinct three-dimensional bipartite configuration of the Xi and the role of specific long non-coding RNAs in eliciting and maintaining this structure. The relative position of specific genomic elements, including genes that escape X inactivation, repeat elements and chromatin features, will be reviewed. Finally, we will discuss the position of the Xi, either near the nuclear periphery or the nucleolus, and the elements implicated in this positioning.This article is part of the themed issue ‘X-chromosome inactivation: a tribute to Mary Lyon’.
Highlights
Mammalian X-chromosome inactivation (XCI) results in the random silencing of one of the two X chromosomes in females early in development in order to ensure a balance in the dosage of X-linked gene expression between the sexes [1]
While significant differences exist between mammalian species in terms of the timing and events associated with the onset of XCI, one unifying theme is that XIST RNA molecules coat the inactive X chromosome (Xi) in cis and recruit chromatin modifiers that lead to the silencing of most of the genes along its length [4,5,6]
It should be noted that the size of topologically associating domains (TADs) is similar to that of interconnected chromosomal regions previously described as chromatin domain clusters (CDCs) based on observations made using microscopy studies, no formal correspondence has been shown to exist between TADs and CDCs [40,41]
Summary
Mammalian X-chromosome inactivation (XCI) results in the random silencing of one of the two X chromosomes in females early in development in order to ensure a balance in the dosage of X-linked gene expression between the sexes [1]. While significant differences exist between mammalian species in terms of the timing and events associated with the onset of XCI, one unifying theme is that XIST RNA molecules coat the inactive X chromosome (Xi) in cis and recruit chromatin modifiers that lead to the silencing of most of the genes along its length [4,5,6]. A lot of research has been focused on gaining a better understanding of the mechanisms behind XCI and the structural nature of the Xi, because it is inherently interesting, but it serves as a useful model for understanding gene regulation in general, and has implications for various disease states. The process of XCI and the central role of the lncRNA XIST have been previously reviewed and are further addressed in other articles in this issue [6,7,8,9]. We will consider the position of the Xi within the nucleus
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
