Cell and Molecular Biology of DNA Methyltransferase 1 - International Review of Cell and Molecular Biology - page 34

6.2. De novo methylation mechanisms in animals
Although de novo methylation in mammals occurs throughout development, it
is concentrated during gametogenesis and early postimplantation development
when the nuclear genome acquires high levels of CpGmethylation. There are
a number of distinct requirements for de novo methylation-imprinted DMD
sequences in the mammalian germ line, in particular, DNMT3A, DNMT3L,
and KDM1B proteins are required for de novo methylation at imprinted loci in
germ cells ( Bourc'his et al., 2001; Ciccone et al., 2009; Kaneda et al., 2004 ).
Importantly, interactions betweenDNMT3A andDNMT3L as well as certain
chromatin modifications are required for the de novo methylation process in
mammals. This process is not only exclusive to imprinted DMD sequences
but also occurs at other genomic locations. Interestingly, although there are
DNMT3A orthologs in plant species that mediated de novo methylation,
whether viaRdDMor otherwise, there is not a DNMT3L ortholog. This sug-
gests that the fundamental mechanisms of de novo methylation are different
between plants and mammals.
Although the catalytic process of de novo methylation may be different
between plants and mammals, molecular events leading to the crucial
DNMT3A-DNMT3L interaction and resultant de novo methylation in
the mammalian germ line share features with the RdDM mechanism iden-
tified in Arabidopsis . piRNAs are 26-32 nt in length and have been found in
mammals, zebrafish, and Drosophila , but not in plants. piRNAs map to
transposon-encoding regions. piRNA-containing complexes are proposed
to guide the de novo DNA methylation machinery to transposon sequences,
and this role is analogous to that of the AGO4/6-siRNA complexes in
RdDM and transposon suppression ( Dalakouras and Wassenegger, 2013 ).
Tudor-domain-containing proteins-Piwi associations are essential for ret-
rotransposon repression. Piwi proteins belong to the ARGONAUTE
superfamily. The requirement of sRNAs and ARGONAUTE proteins is
a conserved mechanism for de novo DNA methylation in mammalian male
germ cells and plant RdDM.
7. CONCLUDING REMARKS
In summary, the apparent divergent roles of DNMT1 underlines the
importance of maintenance methylation in a wide range of cellular processes
such as cell-cycle regulation, DNA repair, genomic stability, telomere main-
tenance, and cell differentiation. Recent research on DNMT1 has provided