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kangaroo, and others exhibiting random X inactivation, like human women
(
Deakin, Chaumeil, Hore, & Marshall Graves, 2009; Okamoto, Otte, Allis,
Reinberg, & Heard, 2004; Okamoto et al., 2011
). In the mouse, these two
forms of X-chromosome inactivation (XCI) exist and occur in non-
overlapping developmental stages and tissues. While random XCI is the
prominent form of inactivation in female somatic tissues, paternal XCI is
specific to preimplantation embryos, and this choice is maintained in extraem-
bryonic lineages, such as the placenta, after implantation (
Fig. 9.2
). Parental X
asymmetry is lost in embryonic tissues just before implantation, as the inactive
paternal X is reactivated in the inner cell mass of the blastocyst to allow
subsequent random choice to inactivate the maternal or the paternal chromo-
some (
Okamoto et al., 2004
). Both imprinted and random XCI in mouse
depend upon a genetically defined region, named the X-inactivation center,
which notably encodes the
cis
-acting determinant of X inactivation, the
Xist
long noncoding RNA (
Augui, Nora, &Heard, 2011
). In imprinted XCI, the
Xist
gene is only expressed from the paternal X chromosome, while in random
XCI, clonal cell populations express
Xist
from either the maternal or the
paternal allele.
Despite avid search for an epigenetic feature inherited from the gametes,
the nature of the imprint responsible for the differential treatment of the two
parental X chromosomes, while they unite within the same ooplasm after
fertilization, is yet to be discovered. The oogenesis-derived imprint prevents
Xist
expression from the maternal allele, while the spermatogenesis-derived
state promotes, actively or by default, paternal
Xist
expression. Interestingly,
the refractory mark of the maternal X chromosome is acquired during
oocyte growth at the same time as autosomal ICRs acquire their DNA
methylation-dependent imprint (
Bourc'his et al., 2001; Tada et al.,
2000
). However, no perturbation of imprinted XCI is observed in embryos
derived from the fertilization of DNA methylation-free oocytes even when
Xist
transcription is genetically abolished on the paternal X chromosome
(
Chiba et al., 2008
). Of note, a maternally provided
trans
-acting factor,
RNF12/RLIM, was shown to be required for paternal
Xist
upregulation
and paternal XCI in preimplantation embryos and extraembryonic tissues
(
Shin et al., 2010
). However, while it may act as a facilitating factor for
XCI, it does not explain why the maternal X chromosome, which is
exposed to the same maternal factors, is unable to express
Xist
.
Transcriptional asymmetry between the parental X chromosomes could
play a role in the initial choice to inactivate the paternally derived X chro-
mosome. One hypothesis proposes inheritance of a predetermined state of
