Biology Reference
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(human homologue of mouse Blimp1) (
Gyory, Wu, Fej
ยด
r, Seto, &Wright,
2004
), and the key developmental regulators
Oct3/4
and
Nanog
(
Epsztejn-
Litman et al., 2008; Feldman et al., 2006; Yamamizu et al., 2012
). G9a is
targeted to the promoter of the transcription factors
Oct3/4
and
Nanog
,
where it deposits H3K9me2 and allows the recruitment of HP1 and
Dnmt3a/b. Gene silencing of
Oct3
/
4
and
Nanog
is tightly controlled by
the joint action of APC/Cdh1-mediated degradation of G9a by the
proteasome and removal of the H3K9me2 mark from their promoters by
the JMJD2A and JMJD2C KDM (
Loh et al., 2007; Wang et al., 2010;
Whetstine et al., 2006
). Indeed,
Jmjd2c
KO in mice results in down-
regulation of
Oct3
/
4
,
Nanog
, and
Sox2
mRNA (
Wang et al., 2010
), whereas
G9a
KO aberrantly prolongs expression of these genes up to embryonic day
7.5 (
Yamamizu et al., 2012
). Both mutant mouse models show develop-
mental defects, suggesting that proper control of G9a-mediated gene silenc-
ing is crucial for the embryo. In fly,
dG9a
was shown to be a suppressor of
position effect variegation (
Mis et al., 2006
), and although
dG9a
mutant flies
show minor developmental defects and are viable (
Seum, Bontron, Reo,
Delattre, & Spierer, 2007; Seum, Reo, et al., 2007; Stabell et al., 2006
), such
role in gene regulation in the embryo could apply. In fact,
dG9a
over-
expression affects transcription of genes involved in the pupal eye formation
(
Kato et al., 2008
). In plants, the SUVR proteins are the most closely related
to G9a (
Baumbusch et al., 2001; Thorstensen et al., 2006
), but so far, they
have been described to function essentially in the repression of transposons
and ribosomal DNA (rDNA) (
Thorstensen et al., 2006; Veiseth et al., 2011
).
2.1.4 HP1
Given its affinity for H3K9 methylated residues, involvement of HP1 for
gene silencing is anticipated (
Bannister et al., 2001; Lachner et al., 2001
).
HP1 can induce compaction of targeted loci (
Verschure et al., 2005
) with
heritability of the repressed state over mitotic division (
Ayyanathan et al.,
2003
). Indeed, artificial targeting of exogenous HP1
a
to a specific locus
induces increased H3K9me3 overtime which can be maintained through
cell division even in absence of further exogenous
HP1a
expression
(
Hathaway et al., 2012
). However, it is now clear that HP1 isoforms, which
show different localizations within the nucleus (
Minc, Allory, Worman,
Courvalin, & Buendia, 1999
), do not completely share redundant function
(
Cammas, Janoshazi, Lerouge, & Losson, 2007
). Some HP1 isoforms are
required for either promoting or repressing transcription, or both (
de
Wit, Greil, & van Steensel, 2007; Vermaak & Malik, 2009
). Indeed, there
