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includes progressively more genes toward more caudal parts of the embryo,
along with the sequential activation process (temporal collinearity, like
Russian dolls; see
Fig. 4.1
). In this chapter, we discuss recent insights con-
cerning both the epigenetic and the 3D chromatin organization of
Hox
clusters, and in particular how these variables may help translating a specific
genomic topology into diverse collinear transcriptional programs.
3. THE MANY FACES OF COLLINEARITY
During
Drosophila
embryogenesis, the
labial
(
lab
) gene, located at one
extremity of ANT-C, is the most anteriorly expressed
Hox
gene, whereas
Abd-B
, a gene located at an extremity of BX-C, is active in the most pos-
terior part of the embryo (
Figs. 4.1 and 4.2
;
Kosman et al., 2004
). For their
initial activation,
Drosophila Hox
genes require local enhancers (e.g.,
Maeda
& Karch, 2006, 2010
). At later stages, active and inactive transcriptional
states are maintained by the Trithorax and Polycomb protein complexes
(see below).
In vertebrate embryos, collinear mechanisms are more diverse and
observed in a wide range of developing structures. Collinearity along the
primary AP axis, which is generally considered as the evolutionary most
ancient function (
Duboule, 2007
), can be divided in temporal and spatial
modalities (
Deschamps et al., 1999; Deschamps & van Nes, 2005; Kmita
& Duboule, 2003
). These collinear modalities are implemented at all four
paralogous gene clusters. The first
Hox
gene activity is detected early on,
in mouse embryos at embryonic stage 7.2 (E7.2), when the 3
0
-located group
1
Hox
genes are activated in the primitive streak (
Fig. 4.1
). In chick embryos,
early activation is also observed in gastrulating mesoderm cells (
Iimura &
Pourquie, 2006
). In a temporal sequence,
Hox
genes are subsequently acti-
vated one after the other (the “
Hox
clock”;
Duboule, 1994
), up to the most
5
0
-located group 13 genes at around E8.5.
Hox
gene activity in vertebrates is maintained up to the stage of
somitogenesis and later, which results in domains where the transcription
of increasingly more
Hox
genes overlaps (
Fig. 4.1
). This process coincides
with axial elongation and the accompanying segmentation clock
(
Pourquie, 2003
), and hence, both clocks must be tightly coordinated to
achieve proper body patterning. In Amphioxus, both temporal and spatial
collinearities are observed as well, thus confirming that these mechanisms
are already present in primitive vertebrates and predated the genome dupli-
cation events (reviewed in
Holland, Holland, & Gilland, 2008
). Indeed,
