Abstract
Early in development, placental and marsupial mammals harbouring at least two X chromosomes per nucleus are faced with a choice that affects the rest of their lives: which of those X chromosomes to transcriptionally inactivate. This choice underlies phenotypical diversity in the composition of tissues and organs and in their response to the environment, and can determine whether an individual will be healthy or affected by an X-linked disease. Here, we review our current understanding of the process of choice during X-chromosome inactivation and its implications, focusing on the strategies evolved by different mammalian lineages and on the known and unknown molecular mechanisms and players involved.
Highlights
Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK
Dosage compensation happens in XX individuals, but instead occurs via the transcriptional silencing of one of the X chromosomes, a process known as X-chromosome inactivation (XCI)
At the molecular level, imprinted and random XCI share some mechanistic features: both are regulated by a region on the X chromosome named the “X-inactivation centre”, Xic and both are associated with the action of long non-coding RNAs that coat the X chromosome in cis and are proposed to direct gene silencing–for a recent review see [24]
Summary
Different mammals have developed distinct strategies to accomplish X-linked dosage. X-linked dosage compensation. At the late blastocyst stage, inactivation of the is a first wave of XCI following zygotic genome activation results in the exclusive Xp inactivation maintained in the extra-embryonic lineages, but reversed in the cells that will give rise to of the Xp (Figure 1). Early studies in trophoblast cells argued that the Xp is preferentially inactivated in this extra-embryonic tissue [16,17]; subsequent allele-specific analyses have. At the molecular level, imprinted and random XCI share some mechanistic features: both are regulated by a region on the X chromosome named the “X-inactivation centre”, Xic (though non-homologous between marsupials and placental mammals) and both are associated with the action of long non-coding RNAs (lncRNAs) that coat the X chromosome in cis and are proposed to direct gene silencing–for a recent review see [24]. A recent methylome study in koalas found that the DNA methylation landscape upstream of Rsx showed a XX-specific pattern [29], consistent with another study in the opossum [30], altogether raising the possibility of Rsx being the functional analog of eutherian Xist
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