Biology Reference
In-Depth Information
Spermatozoa
Embryo
Zygote
PGCs
Global
5mC
levels
Epiblast
Placenta
Oocyte
PGCs
Blastocyst
ICM
E7.5
E13.5
Birth
Fertilization
E3.5
Embryo
Figure 2.4 Reprogramming of DNA methylation during mouse development. The
graph depicts the variations in global DNA methylation levels during mouse develop-
ment. Global levels are extrapolated from immunofluorescence and genome-wide stud-
ies and do not necessarily reflect the dynamics of all individual sequences. PGCs lose
global DNA methylation until E13.5. Methylation is then restored in a sex-dependent
manner before birth in spermatozoa and after birth during oocyte growth. After
fertilization, the paternal genome (blue line) undergoes rapid erasure of 5mC and
the maternal genome (red line) undergoes slow erasure to reach a low point in the blas-
tocyst. Intermediates of demethylation (5hmC, 5fC, 5caC, blue dotted line) appear on
the paternal genome and are gradually diluted during preimplantation development.
After implantation, DNA methylation levels increase in the embryonic tissues derived
from the epiblast and to a mild level in extraembryonic placental structures.
recruited by default to CpG-poor regions and to a small set of CpG islands
(
Fig. 2.4
). There are, however, sequences that escape demethylation after fer-
tilization, in particular, imprinted loci and repeats such as intracisternal A par-
ticles (IAPs) (
Lane et al., 2003
), L1Md_A elements (
Smith et al., 2012
), and
LTR ERV1 elements (
Guibert, Forne, & Weber, 2012
). There is also an
unanticipated high number of CpG islands that maintain oocyte-derived
DNA methylation in preimplantation embryos (
Borgel et al., 2010;
Kobayashi et al., 2012; Smallwood et al., 2011; Smith et al., 2012
). Many
of these regions do not maintain maternal-specific DNA methylation after
implantation because they resolve to unmethylation (
Smith et al., 2012
)or
because paternal alleles undergo
de novo
methylation at the time of implanta-
tion (
Borgel et al., 2010; Proudhon et al., 2012
), indicating that gametic DNA
methylation rarely translates into imprinted methylation.
