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additional genes (
Soshnikova & Duboule, 2009
). During spatial collinearity,
that is when the regulatory programs are maintained in later stage embryos,
similar domains of histone modifications are present along the primary AP
axis (
Fig. 4.5
C, anterior trunk). H3K4me3-marked domains coat active
Hox
genes, with notable enrichments at the promoters. In contrast, contiguous
H3K27me3-marked domains remain over
Hox
genes that are still inactive
(
Noordermeer et al., 2011
). Therefore, these mutually exclusive domains
demarcate
Hox
genes during both their initial temporal collinear activation
and their subsequently maintained states of activities.
Fully inactive
Hox
clusters may carry two different patterns of histone
modifications. In differentiated cells where all
Hox
genes are constitutively
repressed, such as in the fetal brain, H3K27me3-marked domains coat the
entire gene clusters, along with very low amounts (if any) of H3K4me3
(
Fig. 4.5
C, forebrain;
Noordermeer et al., 2011
). In pluripotent embryonic
stem (ES) cells, where
Hox
genes are also inactive, moderate levels of
H3K27me3 modifications coat the full gene clusters too, yet considerable
H3K4me3 signals are detected over
Hox
gene promoters (
Soshnikova &
Duboule, 2009
). In ES cells, such “bivalent” domains are a common feature
of promoters for genes that encode developmental regulators. They are
thought to maintain a repressed—yet transcriptionally competent—state
of activity (
Azuara et al., 2006; Bernstein et al., 2006
). This bivalent chro-
matin state at
Hox
promoters is not observed in
Drosophila
, though the simul-
taneous occupancy of PREs by Polycomb and Trithorax components may
provide a similar flexibility in responsiveness (
Papp & Muller, 2006;
Schuettengruber et al., 2009
).
The recruitment of Polycomb and Trithorax complexes to mammalian
Hox
gene clusters is not well understood (
Beisel & Paro, 2011;
Schuettengruber & Cavalli, 2009
). While some examples of mammalian
PREs have been reported (
Mendenhall et al., 2010; Sing et al., 2009;
Woo, Kharchenko, Daheron, Park, & Kingston, 2010
), a comprehensive
understanding of which genomic feature(s) help recruit Polycomb is lacking.
Three nonexclusive mechanisms have been proposed so far. First, PRC2
would associate with a variety of sequence-specific DNA binding factors
(reviewed in
Schuettengruber & Cavalli, 2009
). For example, DNA binding
of the mammalian PHO ortholog YY1 may target Polycomb to a specific
region in the human
HoxD
cluster in mesenchymal stem cells (
Woo
et al., 2010
). Furthermore, the REST and SNAIL transcription factors
may promote the deposition of H3K27me3 on selected promoters in a neu-
ral precursor cell line (
Arnold et al., 2012
).
