Biology Reference
In-Depth Information
This increased diversity and complexity in collinear programs has been
hypothesized to require a strict topological organization of
Hox
clusters as
observed, for example, in mouse (discussed in detail in
Duboule, 2007
).
In this model, split and fragmented clusters are unable to implement tempo-
ral collinearity. In contrast, some basic traits of spatial collinearity can be
achieved, which thus appear to be more gene-autonomous. The temporal
process necessitates an intact and well-organized gene cluster, as well as some
global regulatory influences located outside of it. The duplication of this
“consolidated” organization in primitive vertebrates, following the 2R
events, may have provided a window of opportunity to evolve new collinear
programs by simply positioning strong regulatory elements in the neighbor-
hoods of the gene clusters. This is supported by the genomic organization of
both the
HoxD
and the
HoxA
clusters, which are surrounded by large
gene deserts containing conserved regulatory elements (
Lee, Koh, Tay,
Brenner, & Venkatesh, 2006; Lehoczky, Williams, & Innis, 2004
). These
newly acquired collinear programs in turn may have induced a further struc-
turing phase, leading to the observed difference between these genomic loci
in vertebrates and early chordates (
Fig. 4.2
).
4. ARE POLYCOMB AND TRITHORAX MEDIATORS OF
COLLINEARITY?
For embryonic structures to be properly patterned,
Hox
gene tran-
scription must be tightly regulated. In
Drosophila
, the spatial succession of
expression domains requires a regulatory mechanism that can act as a switch.
Yet at the same time, collinear activation of these genes ought to be dynamic
and should allow sufficient selectivity among these closely spaced transcrip-
tion units. Protein complexes belonging to two groups with opposing func-
tions regulate and maintain
Hox
gene activity and may thus fulfill some of
these requirements. Polycomb group proteins can maintain the repressed
state of these genes, whereas Trithorax group proteins maintain their active
state. Both Polycomb and Trithorax group proteins exert their function
through modifications of histones, thereby inducing variable states of chro-
matin compaction. Mutations in genes from either group can result in
homeotic transformations, indicating their importance for
Hox
gene regu-
lation (
Fig. 4.5
A; reviewed in
Paro, 1990; Schuettengruber et al., 2007
).
Proteins belonging to both groups are found in many multiprotein com-
plexes (
Fig. 4.5
A).
Drosophila
contains three major classes of Polycomb com-
plexes: PRC2, PRC1, and PhoRC (
Bantignies &Cavalli, 2011; Schwartz &
