515Ross 2013 ). Significance of unique parent-of-origin epigenetic marks differs
across vertebrates. Normal mammalian development requires genomes from
both parents (McGrath and Solter 1984 ; Surani et al. 1984 ) because only this
combination assures functional expression of imprinted genes carrying paren-
tally created epigenetic marks. Such imprinting marks are maintained in the
soma and are erased only during germline reprogramming in primordial germ
cells in the embryo (reviewed in Hajkova 2011 ; Leitch et al. 2013 ). In contrast,
zebrafish and Xenopus can produce viable uniparental diploid progeny demon-
strating epigenetic equality of parental genomes (Cheng and Moore 1997 ).
As some parental epigenetic marks are retained while others are erased, it has
been proposed that reprogramming (i.e., erasure and rebuilding of marks) is bal-
anced with inheritance (i.e., maintenance of parental epigenetic marks) (Gill
et al. 2012 ). To remain within the scope of this chapter, we will focus on erasure
of parental epigenetic marks, which we can be seen as a special category of
parental products, which are eliminated at different phases of development.
Specifically, we will focus on two events during mammalian OET: (1) clearance
of parental DNA methylation after fertilization and (2) loss of parental histone
modifications during OET. For more details on parental imprinting in verte-
brates, the reader is referred to Chap. 12.
10.4.1 Loss of DNA Methylation
Vertebrate DNA methylation (reviewed in Schubeler 2015 ; Li and Zhang 2014 )
employs addition of a methyl group at the carbon 5 of a cytosine followed by gua-
nosine (CpG). This methylation is symmetrical (i.e., occurring also on the cyto-
sine complementary to guanosine in the CpG context) and maintained. DNA
methylation is created by de novo DNA methyltransferases (DNMT3 family),
which operate on non-methylated substrates. Subsequently, CpG methylation is
maintained by the maintenance DNA methyltransferase DNMT1, which recog-
nizes hemi- methylated DNA after replication and renews the symmetrical DNA
methylation by placing a 5-methyl cytosine (5mC) on the newly synthesized DNA
strand. Thus, DNA methylation is a classical “epigenetic mark”—a molecular
modification that does not alter DNA sequence but can carry heritable informa-
tion. DNA methylation in vertebrate genomes is widespread. As a consequence of
conversion of 5mC into thymine, which is a frequent mutation, vertebrate genomes
exhibit lower frequency of CpG dinucleotides than expected frequency calculated
from GC content of the genome (Jabbari and Bernardi 2004 ).
While there is an ongoing debate regarding accurate understanding of causes and
consequences of DNA methylation and transcriptional silencing (Schubeler 2015 ),
this is beyond the scope of this chapter. In the common view, DNA methylation is
associated with transcriptional silencing and contributes to (1) genome maintenance
by mediating silencing of parasitic repetitive sequences and (2) control of gene
expression by enforcing a silenced state of a methylated promoter.
10 Clearance of Parental Products