Biology Reference
In-Depth Information
“self-reinforcing loop.” The self-reinforcing as well as the
cis
-acting nature
of siRNA during RNAi-mediated heterochromatin formation suggests that
the whole process is coupled to the chromatin. This is supported by ChIP
experiments, which show the physical association of Ago1 and Rdp1 with
chromatin (
Cam et al., 2005; Volpe et al., 2002
). Recently, DNA adenine
methyltransferase identification methods to identify DNA binding sites
in vivo
were used to show that Dcr1 also associates with heterochromatin
(
Woolcock, Gaidatzis, Punga, & Buhler, 2011
). This RNAi-mediated het-
erochromatin model also applies to the centromere-like repeats in the mat-
ing locus and to the subtelomeric regions (
Cam et al., 2005
).
Whether a similar or related RNAi-dependent mechanism exists in
mammals is debatable. For example, there is no direct homolog of Chp1
identified so far in mammalian cells, although it is reasonable to believe that
a chromodomain-containing member, like those related to the CBX family,
could potentially fulfill a similar role. Furthermore, although the major and
minor tandem satellite repeats in the mammalian genome can potentially
generate dsRNA (
Martens et al., 2005
), how and whether these dsRNA
molecules are processed has not been addressed.
3.3. Maintenance of heterochromatin throughout the cell cycle
DuringDNA replication, the chromatin is assumed to be drastically perturbed
by the passage of the DNA replication machinery. With this, two main ques-
tions arise: (i) How is the heterochromatin propagated during S-phase? (ii)
How can such a close structure be amenable to remodeling, DNA synthesis,
and recondensation? Indeed, constitutive heterochromatin remains silent
throughout most of the cell cycle, thanks to the recruitment of a myriad of
factors that confer transcriptional silencing RNA Pol II occupancy at hetero-
chromatin is restricted for most of the cell cycle (
Chen et al., 2008
).
Fission yeast spends most of its time in G2, during which HP1 and Chp2
help in the recruitment and spreading of chromatin modifiers such as
SHREC and mediate the assembly of repressive chromatin refractory to
RNA Pol II transcription (
Grewal & Jia, 2007; Sugiyama et al., 2007
). Dur-
ing mitosis, HP1 is lost from H3K9-methylated heterochromatin through
the phosphorylation of the neighboring serine 10, which creates a “methyl
switch” output (
Kloc et al., 2008
). H3S10P-mediated decrease in the chro-
matin association of HP1 proteins during mitosis serves two functions. The
first one is to allow for the recruitment of the condensin complex, which is
essential for chromosome segregation. The second one is to allow hetero-
chromatic transcripts to accumulate in S-phase by creating a short window
