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Review
. 2011 Aug;130(2):203-15.
doi: 10.1007/s00439-011-1014-9. Epub 2011 Jun 7.

XCI in preimplantation mouse and human embryos: first there is remodelling…

I M van den Berg  1 , R J Galjaard, J S E Laven, J H van Doorninck
Affiliations
Review

XCI in preimplantation mouse and human embryos: first there is remodelling…

I M van den Berg et al. Hum Genet. 2011 Aug.

Abstract

Female eutherians silence one of their X chromosomes to accomplish an equal dose of X-linked gene expression compared with males. The mouse is the most widely used animal model in XCI research and has proven to be of great significance for understanding the complex mechanism of X-linked dosage compensation. Although the basic principles of XCI are similar in mouse and humans, differences exist in the timing of XCI initiation, the genetic elements involved in XCI regulation and the form of XCI in specific tissues. Therefore, the mouse has its limitations as a model to understand early human XCI and analysis of human tissues is required. In this review, we describe these differences with respect to initiation of XCI in human and mouse preimplantation embryos, the extra-embryonic tissues and the in vitro model of the epiblast: the embryonic stem cells.

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Figures

Fig. 1
Fig. 1
Schematic overview of three different steps of XCI in mouse and man. Mouse: in the mouse 2-cell stage embryo, imprinted XCI begins with pinpoint Xist expression from the paternal X. At the 8-cell stage, the Xp chromosome is remodelled (XCR, see text for details) with COT-1 exclusion and epigenetic marks; this remodelled X chromosome becomes inactivated (XCI) at the blastocyst stage. Mouse blastocyst ICM cells reactivate the paternal X while the TE and PrE retain the imprinted form of XCI (see text for more detailed description). The imprinted form of XCI is maintained during development of the placenta, while the epiblast converts to a random XCI mechanism. Human: no data are available for single human 2-cell stage embryos regarding the level and location of XIST expression. At the 8-cell stage most cells have a single pinpoint of XIST expression but whether this is an imprinted XCI is not yet known. Human blastocysts have a full cloud of XIST, COT-1 exclusion, epigenetic marks and mono-allelic expression of a gene adjacent to XIST in a portion of the cells, indicative of XCR and the initiation of XCI (van den Berg et al. 2009). Data on XCI in human placenta point towards a preferential silencing of the paternal allele, although random XCI patterns are often observed. The model hES cell lines to study random XCI are not as good in humans as they are in mice: whereas undifferentiated mouse ES cells have two active X chromosomes and upon differentiation randomly silence one X chromosome, undifferentiated human ES cells are extremely variable in XIST expression and so far three classes have been described (see text). ICM Inner cell mass, TE trophoectoderm, PrE primitive endoderm
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