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chapter, one function of maternal H3K9me2 retention could be the protec-
tion of the maternal pronucleus from the removal of 5mC marks, which
occurs on the paternal pronucleus during the early phase of zygotic devel-
opment (
Nakamura et al., 2006, 2012; Szabo & Pfeifer, 2012
). Heterochro-
matic domains formed by pericentric satellite DNA show some other
striking differences in histone modifications. Maternal pericentric regions
exhibit classical constitutive heterochromatic marks, such as H3K9me3
and the associated heterochromatin protein 1 Beta (HP1
b
), inherited from
the oocyte (
Probst & Almouzni, 2011; Santos et al., 2005
). These features
are not present on paternal pericentric regions, which are originally devoid
of heterochromatic marks after fertilization. At the time of DNA replication,
they acquire a form of facultative heterochromatin, H3K27me3 marks,
under the control of the Polycomb repressive complex 2 (
Puschendorf
et al., 2008
). Accordingly, maternally inherited Polycomb repressive com-
plex 1 proteins specifically label paternal heterochromatin (
Puschendorf
et al., 2008
). Remarkably, abolition of parental asymmetry occurs when
the H3K9 methyltransferase Suv39h2 is inactivated, leading to the acquisi-
tion of a paternal-like status by the maternal heterochromatin, which
becomes similarly coated by H3K27me3 marks (
Puschendorf et al., 2008
).
3.2. Parent-specific DNA methylation fates
Pioneering immunofluorescence studies using antibodies directed against
5mC showed a rapid loss of methylation from the paternal pronucleus
within 5 hours postfertilization, creating a dramatic asymmetry between
the two parental pronuclei before the first S-phase (
Fig. 9.2
;
Mayer et al.,
2000; Rougier et al., 1998; Santos, Hendrich, Reik, & Dean, 2002
).
Site-specific bisulfite analysis, at LINE-1 elements, in particular, suggested
a two-step requirement for this loss, with an active initiation phase,
reinforced by a replication-dependent mechanism of passive demethylation
(
Wossidlo et al., 2011
). Recent studies have demonstrated that the first step
is concomitant with gain of 5hmC on the paternal pronucleus, mediated by a
store of maternally provided TET3 protein (
Iqbal et al., 2011; Wossidlo
et al., 2011
). Zygotic TET3 deficiency leads to the retention of 5mC on
the paternal pronucleus, abolishing global parental differences in cytosine
methylation levels. Transition from methylated to unmethylated
cytosines on the paternal pronucleus seems thus to require an intermediate
conversion step toward hydroxymethylation. How conversion from hydro-
xymethylation to demethylation is achieved is the subject of
intense
