517parental DNA methylation of several promoters progressively decline during
cleavage, resulting in the lowest global methylation levels at MBT and during gas-
trulation (Stancheva et al. 2002 ). The loss of parental methylation of ribosomal
genes and specific protein-coding genes correlates with their activation during
MBT (Stancheva et al. 2002 ; Bird et al. 1981 ). However, finer mapping of DNA
methylation at blastula and gastrula using affinity capture of methylated DNA sug-
gested that parentally methylated promoters can transiently support transcription
(Bogdanovic et al. 2011 ).
Zebrafish genome is extensively methylated, but initial analysis of DNA meth-
ylation during early development did not show the genome-wide changes observed
in mammals (Macleod et al. 1999 ). However, a more detailed study suggested that
reduced DNA methylation occurs postfertilization followed by a rapid increase in
DNA methylation (Mhanni and McGowan 2004 ). This observation is consistent
with later genome-wide analysis by bisulfite sequencing (Potok et al. 2013 ).
Analysis of promoter methylation during ZGA by methylated DNA immunopre-
cipitation (MeDIP) showed that promoters methylated in the sperm become demeth-
ylated in the embryo, while nearly all genes methylated in the embryo are also
methylated in the sperm (Andersen et al. 2012 ).
A comprehensive insight into the genome-wide DNA methylation reprogram-
ming in zebrafish was provided by Potok et al. who performed whole genome
shotgun bisulfite sequencing in germ cells and early embryo stages (2–16-cell,
64-cell, 256-cell (all before ZGA), and sphere stage (after ZGA)) (Potok et al.
2013 ). They found demethylation reaching the lowest level at the 64-cell stage
followed by remethylation occurring at the 256-cell stage and restoration of the
global genome methylation by the sphere stage, which was consistent with earlier
data (Mhanni and McGowan 2004 ). Remarkably, the maternal genome methyla-
tion became apparently remodeled by ZGA to the paternal state (Potok et al.
2013 ). Furthermore, parental DNA methylation prevents precocious expression
of specific genes during ZGA—providing a distinct regulatory role for removal of
parentally deposited DNA methylation (Potok et al. 2013 ).
Taken together, parental methylation is removed to a different extent in verte-
brate early development. Active paternal DNA demethylation in 1-cell embryos is
present in many mammals, while in other vertebrates the loss of parental methyla-
tion is much less dramatic and appears much more restricted. A common theme for
vertebrate early embryos seems to be the loss of parental methylation at promoters
that will be utilized during early development.
10.4.2 Loss of Histone Modifications
Histone modifications serving as active and inactive chromatin marks offer a
unique system for recording additional information concerning the histone-asso-
ciated DNA. The so-called histone code may be used in many roles, such as regu-
lation of transcription or DNA repair (reviewed, e.g., in Jenuwein and Allis 2001 ;
10 Clearance of Parental Products