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of opportunity in which heterochromatin is relatively accessible to RNA Pol
II for transcription of the underlying repeat sequences ( Chen et al., 2008;
Kloc et al., 2008 )( Fig. 1.4 ). This increased transcription during S-phase
coincides temporally with the recruitment of the factors involved in hetero-
chromatin assembly at the repeats. The upregulation of heterochromatin
transcripts occurs preferentially on the antisense strand, and these transcripts
are believed to attract heterochromatin assembly factors to the nascent tran-
scripts of the repeats in cis . Indeed, proteins like Rik1 (a ClrC subunit) and
Ago1 (a RITS complex subunit) are preferentially enriched at heterochro-
matic repeats during S-phase ( Chen et al., 2008 ). At this time, heterochro-
matic repeats harbor paradoxically marks of active transcription, including
H3K36 methylation. Again H3K36 is thought to mediate two functions,
one is to promote transcription and the second one is to subsequently recruit
HDAC silencing activities to heterochromatic repeats for further hetero-
chromatin reconstitution during G2 to coordinately silence heterochro-
matic sequences with cis -acting posttranscriptional gene silencing by
RNAi ( Grewal & Jia, 2007; Sugiyama et al., 2007 ).
Finally, H3K9 methylation stabilizes the chromatin association of RNAi
factors and also engages additional ClrC complexes through the Clr4 chro-
modomain, which is thought in turn to help methylating neighboring,
newly incorporated histones. Altogether, this enables the reacquisition of
an equivalent parental heterochromatic pattern on the newly formed chro-
matin after S-phase ( Zhang et al., 2008 ). Importantly, histone chaperones
themselves might play their part in this process as CAF1 has been shown
to associate with heterochromatin factors ( Quivy et al., 2004 ).
3.4. Targetting heterochromatin
A central and prevailing question in chromatin biology is how does a geno-
mic region “know” that it has to be silenced, or in other words, how are
chromatin modifiers targeted to the correct region. In the case of hetero-
chromatin formation, this question remains largely unresolved. Recently,
it has been shown that heterochromatic ncRNAs can be associated with
chromatin through DNA:RNA hybrid formation ( Nakama, Kawakami,
Kajitani, Urano, & Murakami, 2012 ), which provides a target for the RITS
complex, suggesting that heterochromatic ncRNAs are retained on chroma-
tin via the formation of DNA-RNA hybrids and provide a platform for
RNAi-directed heterochromatin assembly. This further suggests that
DNA-RNA hybrid formation plays a role in chromatin-related ncRNA
functions ( Nakama et al., 2012 ).
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