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transcriptional inertia of the paternal X chromosome from the sperm to the
female embryo (
Huynh & Lee, 2003
). During a process called meiotic sex
chromosome inactivation (MSCI) (reviewed in
Turner, 2007
), the sex body
formed by the partially paired X and Y chromosomes becomes transcription-
ally inactive inmale spermatocytes, via the accumulation of repressive histone
marks, but in a
Xist
-independent manner (
McCarrey et al., 2002
). Delivery
of this silent paternal X chromosome may be responsible for its preferential
inactive state in the embryo. A contrasting hypothesis proposes
de novo
inac-
tivation of the paternal X chromosome after fertilization (
Okamoto et al.,
2005; Patrat et al., 2009
). Using RNA FISH, X-linked genes were shown
to be active on both alleles in the two-cell embryo, followed by reduction
to monoallelic expression from the four-cell embryo, as
Xist
becomes
upregulated on the paternal X chromosome. Moreover, using an autosomal
paternally inherited
Xist
transgene, which inherently does not undergo
MSCI, imprinted
de novo Xist
expression and
cis
silencing of the autosome
carrying the transgenewas observed in preimplantation embryos when pater-
nally inherited (
Okamoto et al., 2005
). This study argues for
de novo
imprinted
XCI in the embryo and suggests that paternal inheritance of
Xist
but not
paternal inheritance of a silenced X chromosome is a determining factor.
Imprinted X chromosome inactivation could thus occur in the mouse as a
result of the intense chromatin remodeling, active DNA demethylation,
and precocious timing of transcriptional activation which characterize the
paternal genome. Combined with gamete-inherited resistance of the mater-
nal X chromosome to express
Xist
, earlier expression of
Xist
or other activa-
tors of XCI from the paternal Xcopy likely explains the origin of imprintedX
inactivation in preimplantation mouse embryos.
5. SCARCE MAINTENANCE OF PARENTAL EPIGENETIC
ASYMMETRY AFTER EMBRYO IMPLANTATION AND
THROUGHOUT ADULTHOOD
At the blastocyst stage, after the extensive reprogramming that drives
the embryonic genome toward the acquisition of pluripotency, most of the
parental asymmetries characteristic of the one-cell stage have disappeared.
Limited parent-specific information is selectively protected, so that a few hun-
dred gDMRs maintain oocyte-specific or sperm-specific DNA methylation,
which notably include the ICRs. The wave of
de novo
methylation that occurs
at implantation eliminates most of these gDMRs. The ICRs represent a small
and unique set of gDMRs that retain parent-specificity throughout life.
