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of these elements may lead to mobilization and induction of mutagenic
insertions. However, certain elements may serve beneficial functions, and
a particular class of LTR elements, the murine endogenous retrovirus-like
(MuERV-L), was recently involved in promoting pluripotent properties in
embryonic cells (
Macfarlan et al., 2012
). Expression of these elements exclu-
sively peaks at the time of major embryonic genome activation, at the two-
cell stage. It is not known whether MuERV-L elements are methylated in
sperm, but if so, their autonomous activation in the embryonic genome
would require prior removal of DNA methylation from their promoters.
Still in relation with pluripotency, TET3 deficiency greatly impairs embry-
onic development potential (
Gu et al., 2011
). This was linked to retention of
DNA methylation at the promoter of
Nanog
and
Oct4
genes, which may
delay the expression of these pluripotency factors from the paternal genome.
4. GLOBAL LOSS AND SPECIFIC RETENTION
OF PARENTAL ASYMMETRIES DURING
PREIMPLANTATION DEVELOPMENT
At the two-cell stage of mouse development, the two parental genomes
become equally involved in transcription to promote full embryonic genome
activation. Moreover, at that time, most of the parent-specific histone-based
differences have been reconciled due to the incorporation of new replication-
dependent histones at the first S-phase. Gametic inheritance of DNA
methylation patterns was reduced during the first-cell stage by an active
paternal-specific demethylation process. Patterns are further reduced by a
progressive loss of DNA methylation occurring equally on the two parental
genomes as the embryo progresses toward the acquisition of pluripotency
(
Fig. 9.2
). However, site-specific mechanisms of protection become fully
operant during this period for the retention of a subset of germline-inherited
differentially methylated regions, which include autosomal imprinted loci.
Another form of parental imprinting coexists, which occurs on a
chromosome-wide level, leading to the systematic silencing of the paternally
inherited X chromosome in females, at least in the mouse model.
4.1. Selective protection of parent-specific DNA methylation
patterns
Early immunofluorescence studies originally revealed the occurrence of
hemimethylated chromosomes at the two-cell stage and their progressive
replacement by unmethylated chromosomes toward the blastocyst stage,
