Biology Reference
In-Depth Information
B
C
A
Gametes
Zygote
Preimplantation
KDM1B
TET3
DNMT3A/3L
ZFP57/KAP1
STELLA
TET3
TET3
D
Post implantation
Genome wide
Post implantation
ICRs
???
Maternal nucleosome
Methylcytosine
Hydroxymethylcytosine
Paternal nucleosome
DNMT3A/3B
Unmethylated cytosine
Nucleosome with no
parental distinction
TF
TF
piRNAs
???
Transcription
H3K9me2/3
H3K4me2/3
Maternally
imprinted
Paternally
imprinted
Figure 9.1 Forces acting toward the establishment and the protection of gametically
inherited DNA methylation marks. (A) DNA methylation establishment in the gametes.
DNMT3A and DNMT3L work in the female and male germlines to establish DNA meth-
ylation profiles genome-wide. In oocytes (upper part, red nucleosomes), this process is
guided, at least in part, by traversing transcription and by the removal of H3K4me2/me3
marks, which can be mediated by the KDM1B histone demethylase. In the developing
sperm (lower part, blue nucleosomes), DNMT3A/3L-dependent DNAmethylation can be
guided by piRNAs. Major remodeling of sperm chromatin will occur in the last stages of
spermatogenesis by histone to protamine exchange (not shown). (B) DNA methylation
loss and protection in the one-cell zygote. Before the onset of the first S-phase,
H3K9me2, which is globally associated with maternally methylated DNA, recruits
STELLA thus preventing TET3 binding. On paternal chromatin, TET3 binds 5mC and con-
verts it to 5hmC, except at certain loci such as paternal ICRs, which are protected by
H3K9me2-dependent STELLA binding. (C) DNA methylation loss and protection during
preimplantation development. DNA methylation is passively lost during this period, fol-
lowing embryonic cell division. Methylated sequences that harbor TGCCGC motifs
escape this passive demethylation through the recruitment of the heterochromatic
ZFP57/KAP1 complex. (D) DNA methylation gain and protection in the early
postimplantation embryo. While de novo DNA methylation is set up genome wide,
mainly via the activity of DNMT3B and to some extent of DNMT3A, some loci are protec-
ted with an unmethylated state. Transcription factor binding and/or H3K4 methylation
marks could protect these regions from the action of DNMT3A/3B. This shielding mech-
anism is likely to be operant genome wide and at ICRs, in particular, leading in this case
to the maintenance of parent-specific DNA methylation.
