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at the 2-cell stage (
Fadloun et al, 2013
). It is therefore intriguing how
retrotransposons are silenced during preimplantation development, since at
the time when their transcriptional activity decreases, H4K20me3 and
H3K64me3 are undetectable from the embryonic chromatin, and
H3K9me3 and DNA methylation seem to decrease, both globally and in
LINEs (
Santos et al., 2002; Smith et al., 2012
). In this sense, the
retrotransposons provide actually an excellent model to address how hetero-
chromatic regions other than pericentric domains are silenced during
embryogenesis and it will be important to determine how such regions are
silenced to start with. LINEs and long terminal repeat retrotransposons
(LTRs) are known to be demethylated immediately after fertilization
(
Lane et al., 2003; Smith et al., 2012; Wossidlo et al., 2010
). Most of the data
available in the literature, including recent reduced representation bisulfite
sequence, suggest that levels of DNA methylation on LTRs and on LINEs
do not increase prior to implantation and therefore alternative mechanisms
are probably in place to silence retrotransposons in the early embryo
(
Smith et al., 2012
). This is in linewith elegant experiments inwhich deletion
of KAP1—which is known to silence endogenous retroviruses through an
H3K9me3/DNA methylation pathway—at several developmental times
revealed that KAP1-directed DNA methylation is dispensable for the silenc-
ing of endogenous retroviruses before E3.5 (
Rowe et al., 2010
). Although it is
well known that retrotransposons are silenced through a piRNAmechanism
in the germ line, the piRNA/Dnmt3L pathway seems not to be active in the
early embryo (
Aravin, Sachidanandam, Girard, Fejes-Toth, & Hannon,
2007; Bourc'his & Bestor, 2004; Carmell et al., 2007; Zamudio &
Bourc'his, 2010
). It is therefore possible that other RNA-mediated mecha-
nisms also regulate transcription and/or silencing of repetitive loci during
early embryogenesis, similar to what it has been shown for pericentromeric
repeats.Recent analyses performed inour lab indicating that very shortRNAs
smaller than 18 nt can regulate expression of LINE elements in the mouse
zygote support such a scenario (
Fadloun et al., 2013
). Thus, it could be that
RNA has a more generalized role in regulating transcriptional activity of het-
erochromatic loci during development.
4. CONCLUDING REMARKS
It is clear from all the stated earlier that the organization of the hetero-
chromatin itself as well as its potential role in regulating gene expression will
have a key role in imparting epigenetic decisions during early development.
