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2009; Feng et al., 2010; Zemach,McDaniel, Silva, &Zilberman, 2010
). Alter-
natively, the mechanism for transcription-associated DNA methylation in the
oocyte could rely on
trans-
acting small RNA species, such as endo-siRNAs
(small interfering RNAs), which are abundant in oocytes (
Watanabe et al.,
2008
). This modewouldmirror the small RNA-dependent pathway of
de novo
methylation observed in the sperm, where other small RNA populations
are involved, the piRNAs (piwi-interactingRNAs) (
Fig. 9.1
A). In this model,
retrotransposon transcripts produced ingameteprecursors asDNAmethylation
is erased would serve as substrates for the production of piRNAs via the slicing
activity of PIWI proteins. PIWIs loadedwithpiRNAs can in turn feedback into
the nucleus to promoteDNAmethylation at the promoters of retrotransposons
by homology-dependent recognition (
Aravin&Bourc'his, 2008; Aravin et al.,
2008
). The mechanism of action by which piRNA/PIWI complexes target
de novo
DNA methyltransferases to retrotransposons in the male germline is
still a matter of intense investigation. Recently, one of the three paternal ICRs,
Rasgrf1
, was shown to acquire DNA methylation via the piRNA pathway,
owing to the presence of a retrotransposon in close proximity to this ICR
(
Watanabe et al., 2011
). However, the two other paternal ICRs acquire
DNA methylation in a piRNA-independent manner, leaving the possibility
open that other DNA methylation targeting systems act at these loci.
Finally, in addition to unequal distribution of methylation, there are also
differences in the sequence motifs enriched for cytosine methylation in the
two mature parental gametes. Indeed, while DNA methylation was thought
to concern only symmetric CG dinucleotide contexts, recent reports have
provided evidence for asymmetric non-CG methylation in the oocyte,
ES cells, and brain (
Arand et al., 2012; Guenatri et al., 2013; Lister et al.,
2009; Proudhon et al., 2012; Smith et al., 2012; Tomizawa et al., 2011;
Xie et al., 2012
). This non-CG methylation is believed to reflect the recent
activity of
de novo
DNA methyltransferases, which methylate cytosines in all
contexts. However, asymmetric cytosine methylation cannot be maintained
by DNMT1 upon cell divisions. Therefore, non-CG methylation probably
only exists in nondividing cells, such as oocytes, or in dividing cell types con-
taining large amounts of
de novo
DNA methyltransferases, such as ES cells,
which will reiteratively establish non-CGmethylation after each replication.
Non-CG methylation is present in the oocyte genome, but not in the sperm
genome, which has lost this methylation type upon the multiple cell divi-
sions that separate prenatal
de novo
DNA methylation from mature sperm
(
Ichiyanagi, Ichiyanagi, Miyake, & Sasaki, 2012
). The function, if any, of
non-CG methylation is still elusive.
