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(
Bilodeau et al., 2009; Cho, Park, Kwon, & Kang, 2012; Lohmann et al.,
2010; Yeap, Hayashi, & Surani, 2009; Yuan et al., 2009
). This set of genes
is also targeted by PcG proteins (discussed again in
Section 3.2
). This suggests
cooperation between different epigenetic repressive pathways for
maintaining the stemness state of ESC (
Azuara et al., 2006; Boyer et al.,
2006
). Furthermore, SETDB1 association with the zinc-finger transcription
factor ZNF274, allows repression of Zinc finger genes (
Frietze, O'Geen,
Blahnik, Jin, & Farnham, 2010
), whereas its association with the serine/thre-
onine kinase Akt/PKB mediates repression of certain transcription factors
such as Forkhead family member (
Gao et al., 2007
). This suggests that
SETDB1 mediates transcriptional silencing of specific sets of genes
depending on its binding partners. Zygotic expression of
Setdb1
begins at
the blastocyst stage, while the maternal transcript is present in the oocyte
and persists throughout preimplantation development (
Dodge et al.,
2004
). It would be of great interest to identify binding partners of SETDB1
that could modulate its targets and thereby its biological output during the
earliest stages of embryo development. Despite this role in euchromatic
regions, one striking feature of SETDB1 is the repression of transposable ele-
ments and repeats in mESC (
Karimi et al., 2011; Matsui et al., 2010
), a func-
tion achieved in cooperation with the corepressor KAP1/Trim28 and HP1
proteins (
Schultz, Ayyanathan, Negorev, Maul, & Rauscher, 2002;
Sripathy, Stevens, & Schultz, 2006
), although the latter appears dispensable
for this function (
Maksakova et al., 2011
). Indeed, even if heterochromatin is
more compacted and silent than euchromatin, there is evidence that tran-
scription of repeats is tightly controlled (
Eymery, Callanan, & Vourc'h,
2009
). SETDB1 is also implicated in the regulation of the structure of pro-
myelocytic leukemia-nuclear body (PML-NBs) and the transcription of its
associated genes (
Cho, Park, & Kang, 2011
). PML-NBs that have been
linked to many cellular processes such as apoptosis, DNA damage responses,
and transcriptional regulation (
Torok, Ching, &Bazett-Jones, 2009
), expan-
ding the many potential biological roles of SETDB1 for proper embryo
development. Altogether, these multiple functions achieved by SETDB1
could therefore explain in part the early phenotype seen in
Setdb1
knockout
mice, which die around 3.5-5.5 dpc (
Dodge et al., 2004
).
2.1.3 G9a
G9a takes part in the control of genes like
Mage-a
(
Tachibana et al., 2002
),
p21/waf1
(
Nishio &Walsh, 2004
), some imprinted genes in the trophoblast
(
Wagschal et al., 2008
), interferon beta through its association with PRDM1
