Biology Reference
In-Depth Information
of H3K9/HP1 components results in developmental defects in most organ-
isms.
Suv39h1
/
2
double knockout (DKO) mice are viable although smaller
in size and exhibit chromosomal defects during meiosis in the germline
(
Peters et al., 2001
), partial loss of DNA methylation on PCH (
Lehnertz
et al., 2003
), and increased tumor risks (
Braig et al., 2005; Peters et al.,
2001
). Embryonic stem cells (ESCs) deficient for
Suv39h1
/
2
can maintain
stemness, proliferate, and show enrichment of H3K27me3 on PCH,
suggesting plasticity between Suv39h1/2 and PcG repressive pathways
(
Peters et al., 2003
). Inactivation of
Suv39h
homologues in other organisms
does not strongly impair their viability as it was shown in
Drosophila
(
Schotta
et al., 2002; Tschiersch et al., 1994
), plants (
Jackson et al., 2002; Naumann
et al., 2005
), or even yeast (
Allshire, Nimmo, Ekwall, Javerzat, & Cranston,
1995
), with the exception of the fungi
Neurospora crassa
, where the mutation
of
Dim-5
results in growth defects and sterility (
Tamaru & Selker, 2001
).
Interestingly, in
Dim-5
mutant, both H3K9 and DNA methylation are
affected, suggesting an interdependency of these two chromatin marks in
this organism (for more detail about the link between DNA and H3K9
methylation, see
Box 8.1
). This suggests that the Suv39h enzymes act prin-
cipally as gatekeeper of genome integrity during development by regulating
constitutive heterochromatin more than affecting gene transcription. Inter-
estingly, a recent report demonstrated the requirement of transcription fac-
tors Pax3 and Pax9 for repression of pericentric transcripts and maintenance
of PCH in mouse embryonic fibroblast (
Bulut-Karslioglu et al., 2012
).
However, whether Pax transcription factors directly interact with Suv39h
enzymes and how they could promote their targeting in a developmental
manner remains an open question. Transcriptional regulation by Suv39h1
was recently pointed out in a report from Alder
et al.,
suggesting that devel-
opmental genes targeted by the PcG proteins in mouse ESCs are repressed in
a Suv39h1-dependent manner in the trophoblast lineage (
Alder et al., 2010
).
Knockdown of
Suv39h1
in cultured trophoblast stem cells (TSCs) resulted
in decreased expression of the TSC key transcription factor
Cdx2
, and
enhanced TSC differentiation. This suggests that, at least during the
blastocyst stage of preimplantation development, Suv39h enzymes could
be required for proper trophoblast formation through specific gene regula-
tion. In plants, SUPERMAN (a C2H2-type zinc-finger protein), which is
required for maintaining boundaries between floral organs in
Arabidopsis
,is
controlled by the Su(var)3-9 homologue SUVH4/KRYPTONITE (KYP).
KYP indirectly represses the
SUPERMAN
locus through the recruitment
of the DNA methyltransferase CHROMETHYLASE3 (CMT3), allowing
