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demonstrated that sex-specific DNA methylation is much more prevalent in
mouse gametic genomes (
Kobayashi et al., 2012; Smallwood et al., 2011;
Smith et al., 2012
). Genome coverage differed between the studies due
to the different techniques employed. All are based on the chemical method
of bisulfite conversion, but on the one hand, the reduced representation
bisulfite sequencing (RRBS) technique enriches for CpG-rich regions such
as CpG islands (CGIs) and in reducing genome size allows deeper coverage
in high-throughput sequencing (
Smallwood et al., 2011; Smith et al., 2012
).
On the other hand, whole-genome bisulfite sequencing (Bisul-Seq) enables
a less biased assessment but at the expense of lower sequencing coverage
(
Kobayashi et al., 2012
). Different cutoffs were used for minimum number
of reads per CpG for subsequent analyses. Moreover, two studies used a
recent cartography of 23,021 CGIs in mouse (
Illingworth et al., 2010
), while
the other one adopted a 100 bp sliding window approach (
Smith et al.,
2012
). These differences in sequencing coverage, thresholds for concluding
whether a CpG is methylated or not, and genomic region classification lead
to different numbers of CpGs, CGIs, or germline differentially methylated
regions (gDMRs) that were counted as methylated in oocyte and/or sperm
(
Table 9.1
).
Globally, these studies confirmed that the sperm genome is more meth-
ylated than the oocyte genome, although the percentage of total CpGmeth-
ylation was variably reported as 25%, 83%, or 90% in sperm and as 15%, 32%,
or 40% in the oocyte, depending on the study (
Kobayashi et al., 2012;
Smallwood et al., 2011; Smith et al., 2012
). Genomic methylation in sperm
is relatively enriched at regions of low to intermediate CpG density,
corresponding to intergenic regions and repeats, especially Intracisternal
A Particle (IAP) and Long Interspersed Nuclear Elements, group 1
(LINE-1) retrotransposons (
Kobayashi et al., 2012; Smallwood et al.,
2011; Smith et al., 2012
). The repetitive nature of these sequences is suffi-
cient to explain quantitative dominance of CpG methylation in the sperm
versus oocyte genome, as retrotransposons account for half of mammalian
genomes (
Rollins et al., 2006
). In contrast, CpG-rich CGIs, genomic ele-
ments typically associated with gene promoters, are more likely to be meth-
ylated in the oocyte than in the sperm. Around a thousand CGIs are
methylated only in the oocyte genome, while between 3- and 17-fold fewer
CGIs may be specifically methylated in the sperm genome, depending on
the study (
Kobayashi et al., 2012; Smallwood et al., 2011
). These numbers
exceed the current estimates for ICRs by far (23) and demonstrate that sex-
specific methylation is a general outcome of
the divergent programs
