Biology Reference
In-Depth Information
cell differentiation, in germline development, as well as in disease (
Albert &
Helin, 2010; Richly, Aloia, & Di Croce, 2011
). A common feature of all
these biological processes is the transition from one developmental state
to another, which is accompanied by major changes in gene expression.
Original genetic studies in various species demonstrated major roles of Pol-
ycomb group proteins in the maintenance of stable repression during differ-
entiation (e.g.,
Hox
genes in flies and mammals and
MADS
box genes in
plants). More recently, however, multiple chromatin immunoprecipitation
(ChIP) experiments in different organisms have revealed thousands of puta-
tive Polycomb targets that are controlled in a cell-type specific manner
(
Bouyer et al., 2011; Consortium T.E.P., 2012; Endoh et al., 2012;
Gerstein et al., 2010; Guti
ยด
rrez et al., 2012; Kwong et al., 2008; Mohn
et al., 2008; Roy et al., 2010
). This data allows us to address the divergent
developmental roles of Polycomb by classifying the Polycomb targets and
considering the specificity of distinct PRC complexes. Finally, we will dis-
cuss the various mechanisms for targeting Polycomb to the chromatin.
3.2.1 Dynamics of core and specific polycomb target sets
On the basis of chromatin profiling experiments, Polycomb targets in
mammals can be classified into several classes: (I) core Polycomb target loci,
co-occupied by PRC1 and PRC2 proteins and labeled by H3K27me3
and H2AK119ub1; (II) PRC2-only targets, marked by H3K27 methylation
and sometimes co-occupied by core PRC2 members; (III) PRC1-only
targets, bound by one or more PRC1 members and harboring
H2AK119ub1. There is a fourth class that includes targets bound by
PRC1 or PRC2 members acting in a Polycomb-independent manner (for
instance, as part of other complexes), which we will not consider here.
Although classification may in part relate to differences in immunoprecipi-
tation efficiencies and definitions of enrichment threshold values, genes in
classes I and II do encode for different biological functions and respond dif-
ferently in ESCs upon induction of differentiation (
Ku et al., 2008
).
H2AK119ub1mediated byRing1 andRnf2 is required for repression of class
I genes as well as for the maintenance of ESC identity. PRC1 activity is,
however, not required for binding of PRC1 proteins to target genes, neither
for compaction of, for example, the HoxB cluster in ESCs (
Endoh et al.,
2012
). Generally, these recent results are in accordance with the first
genome-wide study that compared PRC1/PRC2 co-occupancy in ESCs
and identified common 512 targets (
Boyer et al., 2006
), from which 291
overlap with the 510 class I targets found by Endoh and coworkers
(
Endoh et al., 2012
). In summary, PRC1 and particularly the E3-ligase
