Biology Reference
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2011; Hodges et al., 2009; Laurent et al., 2010; Zhou, Lu, & Tian, 2012
).
Changes in DNA methylation correlating with alternative splicing have
also been reported in insects (
Bonasio et al., 2012; Foret et al., 2012;
Lyko et al., 2010
). Mechanistically, this could be mediated by methylated
DNA-binding proteins that regulate splicing via recruitment of splicing
factors (
Long, Ooi, Yau, & Jones, 2011; Young et al., 2005
). Alternatively,
factors like CTCF, which binds to DNA in a methylation-dependent man-
ner, could link DNA methylation to splicing by causing local pausing of
RNA polymerase (
Shukla et al., 2011
). Another way for generating tran-
script diversity is the use of alternative polyadenylation sites. In 2008, a study
identified an unusual imprinted gene that utilizes alternative polyadenylation
sites in an allele-specific manner (
Wood et al., 2008
). Intriguingly, this cor-
relates with DNA methylation of a CpG island localized between the two
poly(A) sites: hypomethylation of the CpG island correlates with the use
of upstream poly(A) sites, whereas hypermethylated alleles preferentially uti-
lize downstream poly(A) sites. In addition, alternative polyadenylation is lost
in embryos lackingmaternally derivedmethylation imprints. Another similar
case was reported recently (
Cowley, Wood, Bohm, Schulz, &Oakey, 2012
),
and although the mechanisms involved are not clear, this suggests that DNA
methylation could also influence polyadenylation.
4.4. Maintenance of genome integrity
In addition, another well-documented function of DNA methylation is to
repress transcription from transposable elements. These elements, consid-
ered as “parasitic,” have the ability to move in the genome and therefore
need to be controlled to prevent mutagenesis. A big proportion of the meth-
ylated CpGs are found in transposable elements and contribute to maintain
them in a silent state. In mouse embryos lacking DNMT1, transcription
from IAPs, a family of active retrotransposons, is massively increased
(
Walsh, Chaillet, & Bestor, 1998
). Similarly, failure to establish DNA meth-
ylation at transposons in male germ cells of DNMT3L-knockout mice leads
to transposon reactivation and meiotic failure in spermatocytes
(
Bourc'his & Bestor, 2004
). Because of the increased mutability of methyl-
ated CpGs, DNA methylation also serves to permanently silence mobile
elements by mutations. Finally, as it is well established that loss of DNA
methylation leads to increased genome instability (
Dodge et al., 2005; Xu
et al., 1999
), it is also possible that methylation of interspersed transposons
or tandem repeats at centromeric heterochromatin could protect against
