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REVIEWS
Regulation of Xchromosome inactivation by the Xinactivation centre
Sandrine Augui*, Elphge P. Nora* and Edith Heard
Abstract | X-chromosome inactivation (XCI) ensures dosage compensation in mammals and is a paradigm for allele-specific gene expression on a chromosome-wide scale. Important insights have been made into the developmental dynamics of this process. Recent studies have identified several cis- and trans-acting factors that regulate the initiation of XCI via the X-inactivation centre. Such studies have shed light on the relationship between XCI and pluripotency. They have also revealed the existence of dosage-dependent activators that trigger XCI when more than one Xchromosome is present, as well as possible mechanisms underlying the monoallelic regulation of this process. The recent discovery of the plasticity of the inactive state during early development, or during cloning, and induced pluripotency have also contributed to the Xchromosome becoming a gold standard in reprogramming studies.
Homogametic and
heterogametic sexes
In species with sexual dimorphism, the sex that can produce two different types of gametes (X and Y or Z and W) is called heterogametic, whereas the sex that can produce only one type of gamete (X or Z) is called homogametic.
Imprinted
Epigenetic marking of a locus on the basis of its parental origin, which can result in differential expression of the paternal and maternal alleles in specific tissues or developmental stages.
Sex chromosome dimorphism leads to a genetic imbalance between the homogametic and heterogametic sexes, which mammals compensate for by inactivating one of the two Xchromosomes during female development. Although this chromosome-wide silencing process was originally described more than 50years ago (TIMELINE),
the underlying molecular mechanisms remain poorly understood. One of the most intriguing aspects of X-chromosome inactivation (XCI) is that two homologous Xchromosomes are differently treated within the same nucleus. How the inactive state is set up and faithfully transmitted through cell division remains a central question for which answers are only now beginning to emerge. This Review will focus on the recent progress that has been made in our understanding of the initiation of XCI, as well as the reversibility of the inactive state during specific stages of development and in the context of reprogramming experiments.
In mice, which have been the favoured model for XCI studies, there are two waves of...