Biology Reference
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that DNA sequences from both the
otrs
and the central domain are required
for full centromere function (
Folco et al., 2008; Wood et al., 2002
). Inter-
estingly, the role of the
otr
sequences seems to be purely to provide a func-
tional platform for heterochromatin assembly, since centromeres lacking
otr
sequences become functional when an enzyme that drives heterochromatin
assembly is tethered adjacent to the central domain sequences (
Kagansky
et al., 2009
).
It was originally thought that fission yeast centromeres were transcrip-
tionally inert, as a marker gene inserted within centromeric sequence
exhibited classical position effect variegation (
Allshire, Javerzat, Redhead,
& Cranston, 1994; Allshire, Nimmo, Ekwall, Javerzat, & Cranston, 1995
).
This silencing was thought to reflect spreading of heterochromatin over
the inserted gene, thereby blocking access of RNA polymerase II (Pol II).
However, it has been demonstrated that centromeres and
otrs
are transcribed
in both fission yeast and mammals, and that transcript abundance in yeast is
regulated by the RNAi machinery (
Lehnertz et al., 2003; Volpe et al.,
2002
). Most importantly, the transcription of these repeats that triggers the
RNAi machinery is an essential part of the heterochromatin assembly path-
way. Centromeric transcription occurs during S-phase, during a window of
time in which the repressive histone marks at centromeres become diluted
upon DNA replication, allowing Pol II access (
Chen et al., 2008; Kloc,
Zaratiegui, Nora, & Martienssen, 2008
).
3.2. Establishment and assembly of constitutive
heterochromatin
Heterochromatin assembly is a multistep process. Studies from diverse sys-
tems suggest that a common set of structural components contribute to the
construction of the heterochromatin platform. Initial targeting of hetero-
chromatin to nucleation sites seems to be distinct from the subsequent het-
erochromatic spreading and maintenance steps. The strategies that are used
by the cell to target heterochromatin differ depending on the chromosomal
context. Local
cis
-acting sequences can promote the establishment of facul-
tative heterochromatin, as exemplified by retinoblastoma protein and
KRAB-KAP1-mediated recruitment of HP1 and SUV39 proteins
(
Nielsen et al., 2001; Schultz, Ayyanathan, Negorev, Maul, & Rauscher,
2002
). The establishment of constitutive heterochromatin is however most
often related to the presence of repetitive DNA elements. It is rather the
repetitive nature of the genomic regions where heterochromatin assembles
and not
the DNA sequence itself, which functions as a trigger for
