Cell and Molecular Biology of DNA Methyltransferase 1 - International Review of Cell and Molecular Biology - page 5

2.2. Significance of symmetric methylation
The bulk of cytosine methylation in A. thaliana and different mammalian
species is symmetric methylation. Moreover, the majority of 5 0 -CpG-3 0
dinucleotides and 5 0 -CpHpG-3 0 trinucleotides in the nuclear genome of
A. thaliana and mammals are methylated ( Feng et al., 2010; He et al.,
2011 ). What might be the significance of such widespread symmetric meth-
ylation? One possibility is that the majority of symmetrically methylated
sequences function in transcription repression of large eukaryotic genomes.
This relationship has been firmly established in both A. thaliana and different
mammalian species by examining the consequences of significant decreases
in genomic methylation. In A. thaliana , a variety of different gene mutations
result in decreased genomic cytosine methylation, and all of these mutations
result in increases in transcription, particularly transcription from highly
repetitive sequences that are normally heavily methylated ( Cao and
Jacobsen, 2002 ; He et al., 2011; Huang et al., 2010; Jones et al., 2001;
Law and Jacobsen, 2010; Lindroth et al., 2001; Ronemus et al., 1996 ). Sim-
ilar observations concerning the consequences of gene mutations have been
made in the mouse. A notable example is the marked increase in transcrip-
tion from repetitive intergenic IAP retrotransposon sequence elements in
methylation-deficient mutant mice ( Walsh et al., 1998 ). In comparison to
other categories of retroelements (both long terminal repeat (LTR) con-
taining and ones without LTRs), IAP elements are presently active in the
mouse genome, and their ability to retrotranspose can result in new insertion
mutations ( Kazazian, 1998 ). Importantly, methylation of IAPs LTR
sequences is required to squelch their transcription and thus their insertional
mutagenicity ( Walsh et al., 1998 ).
Because of the symmetric relationship of cytosines (methylated or not
methylated) in 5 0 -CpG-3 0 dinucleotides (same sequence on opposite base-
paired strand) and 5 0 -CpHpG-3 0 trinucleotides (opposite 5 0 -CpHpG-3 0 strand
in which H-H 0 base-pairing is Watson-Crick; Fig. 1.1 ), “opposite” cytosines
on both single strands can or cannot be methylated. If both opposite cytosines
are methylated in the 5 0 -CpG-3 0 or 5 0 -CpHpG-3 0 context, this is referred
to as fully methylated DNA. In contrast, if just one of the two opposite cyto-
sines is methylated, this is called hemimethylated DNA. This is not true of
asymmetrically methylated cytosine methylation, where there is only a single
cytosine, methylated or not, in the base-paired triplet ( Fig. 1.1 ). Nonetheless,
fully methylated 5 0 -CpG-3 0 or 5 0 -CpHpG-3 0 sites, as well as methylated asym-
metric sites are all associated with transcriptional repression ( Goll and Bestor,