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Pirrotta, 2007, 2008
). The PRC2 protein complex, besides other functions,
trimethylates lysine 27 of histone H3 tail (H3K27me3), a modification asso-
ciated with transcriptional repression. The H3K27me3 mark can subse-
quently recruit the Polycomb (PC) subunit of the PRC1 complex, which
in turn ubiquitinates lysine 199 of histone H2A (H2AK199ub), a modifica-
tion that helps to induce a compacted chromatin state (see
Section 4.5
). The
PhoRC complex can bind DNA and may associate with the PRC2 com-
plex, though this seems insufficient to explain targeting to all Polycomb tar-
gets (
Wang, Brown, et al., 2004
). In mammals, similar PRC complexes are
present, though with a larger variety in their subunits (
Fig. 4.5
A).
Several Trithorax complexes are present in
Drosophila
and mammals,
which may function as chromatin remodelers, histone methyltransferases,
and histone acetyltransferases (
Mohan et al., 2010; Schuettengruber et al.,
2007, 2011
). In
Drosophila,
the Trithorax (TRX) containing COMPASS-
like complex is required for maintained
Hox
gene activity (
Breen &
Harte, 1991
) and can deposit the activating H3K4me3 histone mark
(
Fig. 4.5
A;
Czermin et al., 2002; Eissenberg & Shilatifard, 2010; Smith
et al., 2004
). In mammals, four COMPASS-like complexes are found, of
which only the MLL1 and MLL2 containing complexes can deposit the
H3K4me3 mark at
Hox
loci (
Wang et al., 2009
).
The distribution of both Polycomb and Trithorax components at
Hox
clusters in
Drosophila
, as well as the presence of H3K27me3 and
H3K4me3 marks, has been determined using ChIP-on-chip (
Fig. 4.5
B;
Schuettengruber et al., 2009; Schwartz et al., 2006
). Large domains of
H3K27me3 coat both the BX-C and the
Antp
and
Scr
genes in embryos
and embryonic cell lines. In contrast, the presence of H3K27me3 marks
at the more anteriorly expressed
lab
,
pb
, and
Dfd
is more gene specific
(
Fig. 4.5
B;
Schuettengruber et al., 2009
). Also, the distribution of PRC1
and PhoRC subunits is restricted to somewhat smaller regions within both
BX-C and ANT-C (
Fig. 4.5
B;
Kahn, Schwartz, Dellino, & Pirrotta, 2006;
Schuettengruber et al., 2009; Schwartz et al., 2006
). These regions generally
overlap with Polycomb Response Elements (PREs), which are defined as
cis
-regulatory elements required to maintain
Hox
gene silencing (
Chan,
Rastelli, & Pirrotta, 1994; Muller & Kassis, 2006; Ringrose & Paro, 2007
).
The nature and function of PREs have been intensively studied at the
Ubx
locus (
Papp &Muller, 2006; Tillib et al., 1999
). Components of the PhoRC,
PRC2, and PRC1 complexes can bind the
Ubx
PREs, irrespective of its state
of transcriptional activity. This behavior may be gene- or cell type-specific
though, since the
Abd-B
PREs, in an embryonic cell line, are bound by
