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control the enzymatic activity of PRC2 complexes differentially (
Ohno et al.,
2008
). As a consequence, the maternal
Esc
contribution is required for
development.
3.1.1.2 Mammals
The mammalian PRC2 homologues are
Ezh1
/
Ezh2
,
Eed
,
Suz12
,
Rbbp4
/
Rbbp7
,and
Pcl1
/
Pcl2
/
Pcl3
(see
Table 8.2
). Homozygous mutations for
Ezh2
,
Eed
,or
Suz12
are lethal in early postimplantation development (
Faust
et al., 1998; O'Carroll et al., 2001; Pasini et al., 2004
), while
Pcl2
mutant mice
are viable but show posterior transformations as the result of
Hox
gene
misregulation (
Li et al., 2011
). Gene expression data from mouse and human
for the two KMT homologues
Ezh1
and
Ezh2
suggest that
Ezh2
is predom-
inant in embryogenesis and in proliferating cells, while
Ezh1
might be more
important for postnatal development (
Margueron et al., 2008; Shen et al.,
2008
). Biochemical characterization has identified differences in the activity
of Ezh1-PRC2 and Ezh2-PRC2, implying a strong chromatin compaction
activity and a comparably weaker H3K27me2/3 KMT activity for Ezh1-
PRC2 (
Margueron et al., 2008; Shen et al., 2008
). We could speculate that
the enzymatic activity of PRC2 is more needed early in development, when
the chromatin is still “young” and changing, so keeping the right set of genes
silent in a dynamic environment would require amore active repressor.On the
other hand, a number of studies using
Ezh2
conditional mutants revealed that
Ezh2 is required for the terminal somatic cell differentiation and in some cases
also for themaintenance of themultipotent or progenitor cell state (reviewed in
Aldiri &Vetter, 2012
). Inmost of these cells,
Ezh2
is coexpressed togetherwith
Ezh1
, so it is difficult to assign roles toone or the other. The developmental role
of Ezh1-PRC2 is therefore still unclear, as it is either masked by the presence of
Ezh2or is not critical, since homozygous
Ezh1
mutantmice are healthy, fertile,
and do not show any transformations (
Ezhkova et al., 2011
). Another compo-
nent of PRC2,
Eed
, does not have paralogs in mammals but instead has four
isoforms, which are associated with three variants of the complex—PRC2,
PRC3, and PRC4. These PRC2 variants show biochemical differences,
as PRC2 and PRC4 are suggested to have the canonical H3K27—and an
additional H1K26-KMT specificity, the biological significance of which
remains unknown (
Kuzmichev, Jenuwein, Tempst, & Reinberg, 2004,
Kuzmichevetal.,2005
).
3.1.1.3 Plants
Homologues of all four core PRC2 members are found in
A. thaliana
:
MEA,
SWN, CLF
(homologues of
Ezh2
);
VRN2, FIS2, EMF2
(homologues of
Suz12
);
the
Rbbp4
homologue
MSI1
; and the
Eed
homologue
FIE
