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target PRC2 for gene repression which is consistent with reported biochem-
ical interactions between REST and PcG proteins (
Dietrich et al., 2012;
Ren & Kerppola, 2011
).
Finally, both PRC2 and PRC1 complexes are independently required
for contraction of the
Kcnq1
imprint cluster and imprinted gene silencing
during early mouse development (
Terranova et al., 2008
), as well for the
formation of facultative heterochromatin at one of the two X-chromosomes
in female mammalian cells (
Plath et al., 2003
). In these processes, noncoding
RNAs (ncRNAs) may target PRC complexes to chromatin. Indeed, over
the past few years an ever-increasing amount of data has been accumulating
on the link between ncRNA and Polycomb repression. A prerequisite for
ncRNA-mediated targeting is RNA-binding affinity by PRC members,
and this has been (so far) reported for the PRC2 members Ezh2 and
Suz12 (
Guil et al., 2012; Kanhere et al., 2010; Ng, Johnson, & Stanton,
2012
), as well as for PRC1 member Cbx7 (
Yap et al., 2010
). Until recently,
only a few of the known ncRNAs have been functionally analyzed and
prominent examples linked to PcG targeting are the HOTAIR ncRNA
responsible for the silencing of the HoxD cluster in mammals (
Rinn
et al., 2007; Tsai et al., 2010
), COLDAIR/COOLAIR required for the
cold-induced silencing of the flowering repressor FLC in
Arabidopsis
(reviewed in
Song et al., 2012
), as well as Polycomb/Trithorax-related
ncRNAs in flies (
Hekimoglu & Ringrose, 2009
). A recent study in mouse
ESC identified the “Polycomb transcriptome” consisting of almost 10,000
PRC2-bound RNAs (
Zhao et al., 2010
). Another report focused on a
subclass of ncRNAs and found 24 of the 226 lincRNAs (large intergenic
ncRNAs) in ESC to be bound by PcG proteins (
Guttman et al., 2011
).
Ng et al. described lincRNA-dependent PcG recruitment in human ESC
(
Ng et al., 2012
). The molecular mechanisms underlying target selection
in
cis
and in
trans
in relation to timing of ncRNA expression remain little
understood. Interestingly, HOTAIR is able to bind to PRC2 and a REST
complex, also containing LSD1 and CoREST (
Tsai et al., 2010
), suggesting
scaffold functions for ncRNAs bridging DNA-binding factors and PRC2.
In all, future work is required to determine the relative contributions of
transcription factors, ncRNAs, and recognition of existing chromatin states
in the
de novo
formation versus maintenance of Polycomb gene repression.
4. CONCLUSION
One role of chromatin silencing mechanisms is in the maintenance of
repressed states through cell division. But this does not mean that this is some
