Biology Reference
In-Depth Information
epigenetic processes contribute to the regulation of gene expression before
and at the time of ZGA is the subject of current investigations.
3.1. Expression of DNA methyltransferases in zebrafish
embryos
DNA methylation is, in general, a negative regulator of gene expression.
It organizes long-term gene silencing events during development such as
X chromosome inactivation, genomic imprinting, and the silencing of
repetitive elements (
Reik, 2007
). Several mechanisms by which DNA
methylation may repress gene expression have been identified (
Klose &
Bird, 2006
): repression may be direct by blocking access of transcriptional
activators to promoters, or indirect through the recruitment of methyl-
binding proteins such as Kaiso, methyl-CpG-binding domain proteins
1-4, and MeCP2; these in turn may recruit corepressors such as histone
deacetylases. Additionally, DNA methyltransferases (DNMTs) themselves
may inhibit transcription through interactions with repressive chromatin
modifiers (
Klose & Bird, 2006; Lee, Kim, Taylor, & Muller, 2010
).
In vertebrates, DNA is methylated on cytosines in CpG dinucleotides, by
DNMTs, which convert
S
-adenosylmethionine to
S
-adenosylhomocysteine.
In mammals, DNA methylation is catalyzed by three DNMTs, among which
DNMT1 directs maintenance of methylation after each cell division, and
DNMT3a and DNMT3b carry out
de novo
methylation during development
and differentiation. DNMT2 enzymes are not thought to have DNA meth-
yltransferase activity but rather seem to methylate RNA.
Zebrafish contains representatives of all mammalian DNMT families,
including Dnmt1, and interestingly, six
dnmt
genes (
dnmt3
-
8
)encoding
orthologs to the mammalian DNMT3 family of enzymes (
Fig. 3.2
A). We
and others (
Wu,Zhang,Hammoud,etal.,2011
) have not found a zebrafish
ortholog of the mammalian DNMT3L enzyme which connects unmethylated
lysine 4 of histone H3 (H3K4) to DNA methylation (
Ooietal.,2007
)andis
involved in imprinting. The zebrafish
dnmt3
-
8
gene products have not been
characterized to date; however, transcript profiles for these genes during
pre-MBT, MBT, and post-MBT development reveal distinct patterns which
mayprovidehypotheses onhowkeydevelopmental genesmight bemaintained
in a repressed state before ZGA (
Fig. 3.2
B).
One can from RNA-seq data (
Aanes et al., 2011
) identify four classes
of
dnmt
expression patterns. (i) Maintenance methylase
dnmt1
mRNAs
are highly abundant in the egg, and strikingly,
dnmt1
is downregulated at
the MBT. (ii) At the MBT,
dnmt3
, not expressed in eggs, is strongly
