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probed the effects on the oocyte development and the maternal contribution
to the embryo. Many mRNAs as well as most of the cellular machinery
(ribosomes, mitochondria, etc.) are inherited from the oocyte (
Poznanski
& Calarco, 1991; Smith & Alcivar, 1993; Wagner, 1972
). Furthermore,
the cytoplasmic components of the oocyte have all the necessary material
to reprogram a somatic nucleus (
Chan, Smith, Egli, Regev, & Meissner,
2012
). Therefore, it would be highly important to directly address the effects
of the lack of these methyltransferases from the earliest stages of develop-
ment. Although with some caveats, the most straightforward way to probe
this is probably through the elaboration of conditional KO in the oocyte.
In summary, histone modifications typical of constitutive heterochroma-
tin in somatic cells are exclusively detected on the maternal chromatin at the
very beginning of development only. They either become undetectable at
the 2-cell stage or are “diluted” upon division until methylation starts to
occur
de novo
globally at least three cell divisions later depending on the
mark. Indeed, the kinetics of reacquisition of these histone methylation
marks seems to be slightly different depending on the histone modification
in question (
Fig. 1.2
). This lack of conventional heterochromatin during the
first divisions following fertilization presumably creates a chromatin envi-
ronment that is permissive for epigenetic reprogramming and a “window
of opportunity” for transcription of heterochromatic regions that are nor-
mally not transcribed such as retrotransposons (see Section 3.5).
2.2. DNA methylation and hydroxymethylation
DNA methylation of cytosines functions in gene silencing (
Goll & Bestor,
2005
). In spite of being a highly differentiated cell, the sperm shows a pro-
moter DNA methylation landscape that resembles globally that of pluripo-
tent ES cells with a few key exceptions (
Farthing et al., 2008
). This feature
has been suggested to reflect the epigenetic reprogramming of the germ line
prior to fertilization and to be important in the transmission of pluripotency
to the embryo. The oocyte shows an overall global hypomethylation status
and does contribute with a number of specific methylated regions, including
differentially methylated regions to the embryo (
Smallwood et al., 2011;
Smith et al., 2012
). Upon fertilization, there is a reduction in global
DNA methylation levels that is specific to the paternal genome (
Mayer
et al., 2000; Rougier et al., 1998
). These conclusions were made mainly
by using a 5-methylcytosine (5mC) antibody in immunostaining, which
clearly reveals a loss of the epitope in the paternal pronucleus. A current
emerging notion is, however, that the extent of this demethylation is lesser
