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ZFP57 when the internal CG motif is methylated. Known ICRs notably
harbor these motifs in multiple copies. By superimposing genetic and
epigenetic information, ZFP57 allows the exclusive recognition of genomic
regions, which are CG-rich and are inherited in the zygote as methylated,
allowing their selective protection against the passive wave of DNA deme-
thylation. Among the 91 sequences bound by ZFP57, possible novel ICRs
are present, provided that they acquire parent-specific methylation patterns
in gametes and subsist throughout life. Some of them were indeed con-
firmed to be new genuine parent-specific gDMRs, persisting throughout
life, like the
Cdh15
ICR. But for a number of ZFP57-bound gDMRs,
parent-specific methylation appeared to be lost after implantation during
embryonic differentiation (
Proudhon et al., 2012
).
Taken altogether, key advances in understanding how DNA methyla-
tion is maintained during preimplantation, from the one-cell zygote to
implantation, could support a two-step model whereby genome-wide pro-
tection against active DNA demethylation occurs on the maternal genome
and specific paternal ICRs via H3K9me2 and STELLA. Subsequent protec-
tion against passive DNA demethylation of distinct loci of maternal and
paternal origin would then occur via ZFP57/KAP1 (
Fig. 9.1
C). Consider-
ing the link between the KAP1 complex and the H3K9 methyltransferase
SETB1 protein, H3K9me2 marks could also be mechanistically linked to
this second protective process. These players appear as key determinants
for the conservation of gametic inherited epigenetic information and, more
specifically, for allowing perpetuation of some parental asymmetries beyond
preimplantation development. However, the greater number of blastocyst
gDMRs compared to the number of ZFP57 binding sites suggests that
additional proteins may be at play. The plethora of zinc-finger proteins con-
taining Kr¨ppel-associated box represent attractive candidates for conveying
additional sequence specificities to the KAP1-mediated retention of gamete-
inherited DNA methylation.
4.2. Imprinted X-chromosome inactivation
In addition to gene-specific imprinting, chromosome-wide imprinting occurs
in early preimplantation embryos, specifically in females. In mammals,
X-linked dosage compensation occurs between XX females and XY males
through the silencing of one of the X chromosome in females. This process
is achieved differently among therian mammals, with some species exhibiting
systematic, imprinted inactivation of the paternal X chromosome, like the
