Biology Reference
In-Depth Information
the human LncRNA HOTTIP has been proposed to associate with the
Trithorax components ASH2L and WDR5 and to activate
HOXA
genes
in
cis
. Knockdown of HOTTIP interfered with the MLL1, WDR5, and
ASH2L distribution over active
HOXA
genes in human foreskin fibroblast
cells (
Chen et al., 2011;Wang et al., 2011
). Such noncodingRNAs have been
reported to act in a similar way at a
DrosophilaUbx
PRE, via the recruitment of
ASH1 (
Sanchez-Elsner et al., 2006
).
In summary, the presence of both H3K27me3 and H3K4me3 marks is
tightly associated with collinear transcriptional programs, through their
dynamic coating of
Hox
clusters. Polycomb complexes are likely instrumen-
tal in these processes, by mediating—or tightening—the repression of
Hox
genes at times and in places where given HOX proteins would be function-
ally detrimental to the developing embryo. Similarly, the Trithorax-
containing COMPASS-like complexes appear instrumental in maintaining
active states of
Drosophila Hox
genes and the deposition of the H3K4me3
mark at mouse
Hox
clusters (
Breen & Harte, 1991; Wang et al., 2009
).
Importantly though, the majority of H3K4me3 in
Drosophila
and mammals
is deposited at active promoters by COMPASS-like complexes, which may
associate with RNA polymerases and contain neither the Trithorax nor the
MLL1/MLL2 subunits (
Ardehali et al., 2011; Lee & Skalnik, 2005, 2008;
Lee, Tate, You, & Skalnik, 2007
). Therefore, deposition of the majority
of H3K4me3 marks at active
Hox
genes may merely be a readout of tran-
scriptional activity, rather than a driving force.
While the functional organization of
Hox
clusters is generally conserved
from
Drosophila
to mammals (
Duboule & Dolle, 1989; Graham et al., 1989
),
the recruitment and distribution of Polycomb and Trithorax complexes at
Hox
clusters thus appears to differ substantially, due to some fundamental
differences in the underlying developmental principles (
Duboule, 1994
).
5. DOWNSTREAM OF POLYCOMB AND TRITHORAX:
A COMPACTED CHROMATIN ARCHITECTURE
Polycomb and Trithorax complexes and their associated histone
modifications may help memorize the various collinear transcriptional states,
through differential compaction (or condensation) of chromatin. Chromatin
compaction as induced by PRC1 has been studied in some detail both
in vitro
and
in vivo
.
In vitro
, the addition of PRC1 leads to the compaction a human
nucleosomal arrays, as determined by electron microscopy (
Francis,
Kingston, & Woodcock, 2004
). This
in vitro
compaction requires the
