Biology Reference
In-Depth Information
show a very strong phenotype, with perinatal lethality and aberrant cerebral
cortex development, suggesting a role for HP1
b
in late stages of development
(
Aucott et al., 2008
). As mentioned earlier, it will be important to probe the
function of the HP1 proteins after fertilization by performing, for example,
conditional KOs in the maternal germ line. This is particularly relevant in light
of the fact that HP1
a
seems to be absent from embryonic chromatin until the
blastocyst stage, whereas HP1
b
is tethered onto embryonic pericentromeric
chromatin as early as in the zygote stage (
Arney et al., 2002; Santenard et al.,
2010; Santos et al., 2005; Wongtawan et al., 2011
). This mirroring temporal
expression patternmight suggest different functions of these twoHP1 isoforms
during epigenetic reprogramming
in vivo
.
Although not strictly a constitutive heterochromatic mark, H3K27me3
has probably a “dual” role during early development. Indeed, it seems to be
able to replace functionally the absence of H3K9me3/H4K20me3 on the
paternal pericentric heterochromatin (
Puschendorf et al., 2008; Santenard
et al., 2010
). The KOs of several of the components of the PRC2 do show
early developmental phenotypes. The catalytic subunit of PRC2, Ezh2, is
required for implantation, and mutant embryos for Ezh2 show defective
growth, poor implantation rates, and gastrulation defects (
O'Carroll et al.,
2001
). The maternal deletion of Ezh2 has a growth retardation effect on
born pups, but the phenotype seems to be rescued by the expression of
the paternal allele (
Erhardt et al., 2003
). The second PRC2 core subunit,
Eed, is necessary for gastrulation (
Faust, Lawson, Schork, Thiel, &
Magnuson, 1998; Shumacher et al., 1996
) and for the maintenance of the
inactive state of the X chromosome in trophoblast cells (
Wang et al.,
2001
). The KO of the third and last core subunit of PRC2, Suz12, shows
a similar phenotype to the
Ezh2
and
Eed
/
mice with lethality occurring
at E8.5 (
Pasini et al., 2004
). All these phenotypes are in line with the obser-
vation that all three subunits are absolutely required for H3K27me3. Dele-
tion of other Polycomb proteins such as YY1 results in preimplantation
lethality and in defective ICM growth (
Donohoe et al., 1999
). It is therefore
very well established that Polycomb proteins play key and essential develop-
mental roles during preimplantation development.
These loss-of-function strategies have established that heterochromatin
(through the di- and trimethylation of H4K20, H3K9, and H3K27) is
important for developmental processes but do not establish the mechanism
by which these modifications confer a cellular effect. Furthermore, several
groups have studied the KO of some of these genes in the germ cells and
showed an effect on spermatogenesis, but only a few/none of them have
