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However, no early embryonic defects have been described. It has also been
observed in
dn
Mouse Embryonic Fibroblasts (MEFs) mutant for Suv39h1/2
that the loss of H3K9me3 was accompanied by an increase of H3K27me3 in,
for example, pericentromeric repeats (
Martens et al., 2005
), which seemed
to compensate for the lack of Suv3-9 activity on these regions. In the mouse
zygote, the Peters lab proposed that there is a hierarchy between the con-
stitutive and facultative heterochromatin at the pericentric and centromeric
regions. In case of the incorrect establishment of H3K9me3 mark in the
maternal pronucleus, H3K27me3 is established as a fail-safe mechanism
to silence these repetitive sequences (
Puschendorf et al., 2008
). However,
the sensing or targeting mechanism for the ability of the PRC2 to deposit
H3K27me3 in this context has not been established yet. It was also not
reported whether the loss of H3K9me3 on the maternal pericentric chroma-
tin had any effect on the recruitment of Suv420H1/2 and thus if there was
any accompanying reduction in H4K20me2/3.
In mammals, there are two genes that code for Suv4-20,
Suv4
-
20h1
and
Suv4
-
20h2
, and they that been genetically inactivated both in isolation and
in combination. The double KO of Suv4-20h1 and Suv4-20h2 mice also
display perinatal lethality, as well as an increase in DNA damage sensitivity,
cell cycle defects and chromosomal aberrations (
Schotta et al., 2004, 2008
).
A potential role for
Suv4
-
20h1/h2
in preimplantation development has not
been reported.
The othermain component of constitutiveheterochromatin isHP1.Mam-
mals have three different HP1 isoforms: HP1
a
,
b
,and
g
in humans (CBX5, 1
and 3, respectively, in mice). The three HP1s contain the same modular struc-
ture: a chromoshadow domain that is involved in protein-protein interactions
(
Nielsen et al., 2001
), a hinge domain that binds ssDNA and RNA (
Muchardt
et al., 2002
), and a chromodomain that recognizes andbinds toH3K9me2/me3
(
Lachner et al., 2001
). An HP1
a
KO has been reported to have no apparent
effect on embryonic development (
Aucott et al., 2008; Brown et al., 2010
).
There seems to be some degree of redundancy among HP1 proteins. Indeed,
the HP1
g
KO did not show any developmental phenotype, and the authors
suggested that the other paralogues of HP1 might compensate for its loss.
The absence of HP1
g
does result, however, in major defects in chromosome
segregation in spermatocytes and leads to severe male sterility (
Naruse et al.,
2007;Takadaetal.,2011
). Perhaps surprisingly, in contrast to the KOmodel,
a hypomorphic mutant for HP1
g
shows high lethality after birth with only 1%
of mice reaching adulthood but with similar effect on spermatogenesis
(
Brown et al., 2010
). Of the three HP1 isoforms, only the HP1
b
KO mice
