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with intermediate methylation states are preferentially used as substrate.
Together, these data suggest that number of modified nucleosomes within
a region likely affects the efficiency of propagation (
Brykczynska et al.,
2010;Xu et al., 2012
). The catalytic activity of the PRC2 complex is inhibited
by H3K4 and H3K36 trimethylation, when residing on the same histone tail
in the nucleosome (
Schmitges et al., 2011; Voigt et al., 2012; Yuan et al.,
2011
), potentially providing means for inhibition of spreading of the
PRC2 repressed state by Trithorax group proteins. Furthermore, indepen-
dent of the stimulatory effect of preexisting H3K27me3, PRC2 activity is
stimulated by high nucleosomal density that is sensed by the VEFS-box
domain of the Su(z)12 protein interactingwith amino acids 35-42 of H3 pro-
truding from the nucleosome core. For PRC1, Psc interacts with nucleo-
somes and self-interacts in cell-fee replication systems thereby forming
oligomeric structures. Since some Psc-chromatin contacts are dynamic
while others are stable, Psc may enable inheritance of PRC1 on chromatin
during replication (
Lo et al., 2012
).
De novo
targeting and propagation may also be in part mediated by inter-
actions of PRC proteins with the underlying DNA. Indeed, fly PcG proteins
interact with specific DNA-binding factors such as PHO that associate with
complex DNA elements termed Polycomb response elements (PREs)
(
Ringrose & Paro, 2007
). Regions around such sites are marked by
H3K27me3 and are co-occupied by Pc, likely due to its CD that has a high
binding affinity to H3K27me3 (
Fischle et al., 2003; Schuettengruber et al.,
2009
). In
Drosophila
embryos, E(z) and Pc proteins, but not H3K27me3,
have been reported to be associated with PREs on recently replicated
DNA, suggesting that these proteins may be directly involved in epigenetic
heritability. In mammals, the role of transcription factors is less understood
and only two PRE-like sequences have been identified up to date (
Sing
et al., 2009; Woo, Kharchenko, Daheron, Park, & Kingston, 2010
). The
role of PHO in targeting is probably not conserved in mammals since
YY1, the mammalian orthologue, is not localized at PRC target genes in
ESCs (
Ku et al., 2008; Mendenhall et al., 2010
). PRC proteins generally
localize at CpG-rich sequences suggesting a possible function of transcrip-
tion factors binding within such elements (
Ku et al., 2008; Zheng, Zhao, &
Mehler, 2009
). Arnold and colleagues revealed a role for Rest in H3K27me3
establishment at specific target sequences in neuronal progenitor cells during
differentiation of ESCs (
Arnold et al., 2012
). Sequences containing Rest and
Snail transcription factors are sufficient for the recruitment of H3K27me3 at
targeted transgenic insertion sites suggesting that transcription factors can
