Biology Reference
In-Depth Information
3. POLYCOMB REPRESSIVE PATHWAYS
3.1. Composition and developmental role of PcG proteins
In recent years, the composition and variety of Polycomb complexes in dif-
ferent cell types and organisms have received substantial attention. Many of
the core components of PRCs have been duplicated during evolution, but
instead of acting as “spare parts” serving redundant functions, these paralogs
acquired different developmental roles during their divergence. In addition,
there are other components that associate with Polycomb complexes (Pol-
ycomb cofactors), which further increase the variety and have an effect on
the functionality and the targeting of the complexes in different cell types.
Remarkably, the divergence of Polycomb complexes is not a rare event in
evolution, since it occurred in plants, flies, and mammals. Below, we will
focus on the composition and developmental roles of PRC1 and PRC2
in three model organisms.
3.1.1 PRC2
3.1.1.1 Drosophila
E(z), Su(z)12, Esc/Escl, and Nurf55 are the core PRC2 components in
Drosophila
(see
Table 8.2
), which together have been isolated as a 600-kDa
complex (
M¨ ller et al., 2002; Tie, Furuyama, Prasad-Sinha, Jane, & Harte,
2001
). Pcl has been identified as part of a bigger Pcl-PRC2 complex (
Tie,
Prasad-Sinha, Birve, Rasmuson-Lestander, & Harte, 2003
), where Pcl
functions as an enhancer of the H3K27 trimethylation
in vivo
(
Nekrasov
et al., 2007
). In
Drosophila
larvae, Pcl facilitates the recruitment of PRC2
to chromosomes (
Savla, Benes, Zhang, & Jones, 2008
). Classical Polycomb
phenotypes related to the misregulation of
Hox
genes have been described
for all PRC2 members and with the exception of
esc
and
escl
, all homozygous
null alleles show larval lethality (
Anderson et al., 2011; Birve et al., 2001;
Duncan, 1982; Phillips & Shearn, 1990; Struhl & Brower, 1982
). According
to the
Drosophila
developmental transcriptome project (
Gelbart & Emmert,
2011; McQuilton, St Pierre, & Thurmond, 2012
), mRNA levels for all
PRC2
genes peak in early embryos, then decline at larval stages and increase
in female but not male adults. The only exceptions are the partially redundant
paralogs
Esc
and
Escl
with
Esc
predominantly expressed in embryos and
Escl
in
late larval/early pupal stages (
Kurzhals et al., 2008
). In addition,
Esc
and
Escl
mRNAs undergo splicing with different efficiencies and the two proteins
