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cluster, whereas the inactive compartment has retracted accordingly
(
Noordermeer et al., 2011
). This bimodal organization leads to a physical
separation both between active and inactive
Hox
genes, and between the
Hox
clusters and their chromatin environments. The 3D compartmentaliza-
tion of active genes may involve activating factors, whose elevated concen-
tration may in turn reinforce the transcriptional outcome and the recycling
of the transcription machinery.
So far, the local compartmentalization of active chromatin has been
reported only in mouse and human
Hox
gene clusters (
Montavon et al.,
2011; Noordermeer et al., 2011; Wang et al., 2011
). It may be that the
MLL1/MLL2 containing COMPASS-like complexes are involved in this
spatial organization, as they specifically mediate H3K4me3 deposition at
these loci (
Wang et al., 2009
). Whether or not active
Hox
genes in
Drosophila
are also organized within such 3D domains remains to be determined. How-
ever, unlike in vertebrates, the expression domains of
Hox
genes in
Drosophila
do not systematically overlap and, hence, 3D compartments, if any, would
need to be more locally restricted.
Unlike other
Hox
loci,
Hoxb13
is separated from the
HoxB
cluster by a
relatively large repeat-containing piece of DNA (
Fig. 4.3
;
Zeltser, Desplan,
&Heintz, 1996
). When inactive, the
HoxB
cluster forms a 3D compartment
that includes all genes, yet the intervening DNA loops out (
Fig. 4.7
A, right).
Upon gene activation, this cluster expectedly adopts a bimodal 3D organi-
zation, which, however, does not include the intervening DNA in either
compartment (
Fig. 4.7
B, right). Interestingly, the temporal and spatial
expression pattern of
Hoxb13
is not affected by the deletion of the rest of
the
HoxB
cluster (
Medina-Martinez, Bradley, & Ramirez-Solis, 2000
),
suggesting that it is regulated autonomously from its closely related
Hox
clus-
ter. In this case, as in
Drosophila
, the proximity to the
HoxB
cluster may help
strengthening the repressive state.
By extension, vertebrate
Hox
clusters may also be organized as dynamic
3D compartments during the implementation of temporal collinearity.
However, a progressive shift of 3D compartments in the same cell lineage
along with time has not yet been reported. While spatial collinearity in
mammals depends—at least in part—upon local enhancers, comparable to
the case of
Drosophila
(
Maeda & Karch, 2010; Tschopp et al., 2009
), tempo-
ral collinearity seems to be guided by a global mechanism, also influenced by
the neighborhood of the gene cluster (
Tschopp et al., 2009
). Noteworthy,
should temporal collinearity rely upon a dynamic shift between local 3D
compartments, this would give a mechanistic ground to the tight association
