Biology Reference
In-Depth Information
BOX 8.1 Interplay between H3K9 and DNA methylation
cont'd
(
Quenneville et al., 2011; Rowe et al., 2010; Schultz et al., 2002
). Targeting to specific
genomic regions is mediated by KRAB-ZNF proteins, like Znf57, which can target
this complex to ICRs when they are methylated, a mechanism suggested to protect
these loci from demethylation during early embryo development (
Quenneville
et al., 2011, 2012; Zuo et al., 2012
). KAP1 therefore acts as a scaffold linking DNA
methylation, H3K9me3 and HP1 binding to specific loci which repressive state
needs to be maintained for proper development. With the hundreds of KRAB-
ZNF proteins encoded by the human genome (
Huntley et al., 2006
), it will be chal-
lenging to understand the contribution of these proteins for targeting KAP1-
repressive complex (and thenDNA and H3K9methylation) to specific genomic sites
during early embryo development.
HP1g, which was recently mapped in HCT116 cells show a localization toward
gene bodies and is thought to be involved in RNA processing (
Smallwood et al.,
2012
). Strikingly, DNA methylation in gene bodies is often associated with tran-
scriptional activity and it has even been suggested to participate in RNA splicing
(
Laurent et al., 2010
); however, it is not known if there is a direct interplay
between these two pathways for achieving this function. Recently, new evidence
was brought for a direct link between H3K9 and DNA methylation, as PGC7 (also
known as Dppa3/Stella) has been shown to bind H3K9me2. Pgc7 is involved in
protecting from active demethylation the maternal genome, marked by
H3K9me2, and several paternally imprinted genes in the zygote (
Nakamura
et al., 2012
). In plants and mammals, DNA methylation can occur on CG, CHG,
and CHH context (where H is either a C, T, or A). In A. thaliana, methylation on
CHG is maintained by a positive feedback loop between the Su(var)3-9 homologue
SUVH4/KYP and DNA methyltransferase CMT3 in order to silence genes and
retrotransposons (
Jackson et al., 2002, 2004
). Indeed, H3K9me1/2 catalyzed by
SUVH4/KYP (the major enzyme responsible for H3K9me1/2 in plant heterochroma-
tin) allows recruitment of HP1, which then allows binding of CMT3 and DNAmethy-
lation. Recently, it was also shown that SUVH4/KYP is required for the chromatin
remodeler DDM1 (decrease in DNAmethylation 1) dependent de novo methylation
(
Sasaki, Kobayashi, Saze, & Kakutani, 2012
). Furthermore, plant SUVH homologs
contain a YDG/SRA domain in their N-terminus that can bind methylated DNA
(
Johnson et al., 2007
), suggesting that methylated DNA can reinforce the silencing
signal by enhancing the recruitment of SUVH enzymes (
Ebbs & Bender, 2006
).
However, the most striking evidence of a direct link between DNA and H3K9
methylation comes from studies in the fungi N. crassa. In this organism, mutation
of DIM-5,aSu(var)3-9 homologue, results in a global loss of both H3K9me3 and
DNA methylation (
Tamaru & Selker, 2001
), similar to what is seen in the DNA
methyltransferase DIM-2 mutants (
Kouzminova & Selker, 2001
), although the lat-
ter does not affect H3K9 methylation. The link between these two marks is HP1,
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