Biology Reference
In-Depth Information
activity of its Ring finger proteins are required in ESCs and during mouse
development for silencing of a rather small but important set of evolutionary
conserved genes encoding for developmental regulators.
Interestingly, from the thousands of Polycomb targets described, only
several hundred genes belong to class I marked by PRC1 and PRC2 loci.
A similar observation was made in
Drosophila
. Several independent
genome-wide experiments identified around 200-400 Polycomb targets
co-occupied by several PcG members (
Guti´rrez et al., 2012;
Schuettengruber et al., 2009; Schwartz et al., 2006
), which roughly corre-
spond to 20% of all H3K27me3 target sites. In a systematic genome-wide
ChIP study, analyzing the chromatin localization of 53 proteins in Kc167
embryonic cells, Filion and colleagues identified five distinct types of chro-
matin (
Filion et al., 2010
). Class I target genes were represented by one chro-
matin type. H3K27me3 only states were found in one of the two actively
transcribed chromatin types, suggesting that class II genes might be partially
associated with active chromatin. Furthermore, upon removal of Polycomb,
the number of upregulated genes (derepressed targets) is significantly lower
than the number of targets bound, and most of the misexpressed genes are
“classical” Polycomb targets or class I targets (e.g.,
Hox
genes, Wnt-, Fgf-,
Tgf-signaling genes, and other developmental regulators) (
Bracken,
Dietrich, Pasini, Hansen, & Helin, 2006; Ezhkova et al., 2011; Posfai
et al., 2012
). Therefore, the role of class II and III target loci remains to
be determined. Are they serving as a buffer of regulation or perhaps as a
structural component of the chromatin landscape?
3.2.2 Mechanisms of polycomb recruitment
Over the years, a lot of effort has been put into revealing the targeting mech-
anism of PRCs and propagation of the modified state. The classical model of
epigenetic inheritance of the H3K9 methylated state by HP1 proteins recog-
nizing the methylated histone as well as interacting with H3K9 HMTs fueled
the field (
Jenuwein & Allis, 2001
). Seminal work by Margueron et al. dem-
onstrated that binding of the PRC2 component ESC/EEDvia itsWD40 pro-
peller toH3K27me3 stimulates E(Z)/EZH2 to catalyze trimethylation of the
unmodified substrate (
Margueron et al., 2009
). Together with work by
Hansen et al. (2008)
, these data provided, in principle, a mechanism for epi-
genetic inheritance. More recent work indicates that reestablishment of
H3K27me3 levels (and also for H3K9me3) does not occur during replication
but gradually during subsequent cell cycle stages (
Xu, Wang, Chen, & Zhu,
2012
). Importantly, instead of newly incorporated histones, parental histones
