Journal
MOLECULAR AND CELLULAR BIOLOGY
Volume 28, Issue 11, Pages 3713-3728Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.02263-07
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Funding
- Biotechnology and Biological Sciences Research Council [BBS/E/B/0000C151] Funding Source: researchfish
- BBSRC [BBS/E/B/0000C151] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BBS/E/B/0000C151] Funding Source: Medline
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The Kcnq1ot1 antisense noncoding RNA has been implicated in long-range bidirectional silencing, but the underlying mechanisms remain enigmatic. Here we characterize a domain at the 5' end of the Kcnq1ot1 RNA that carries out transcriptional silencing of linked genes using an episomal vector system. The bidirectional silencing property of Kcnq1ot1 maps to a highly conserved repeat motif within the silencing domain, which directs transcriptional silencing by interaction with chromatin, resulting in histone H3 lysine 9 trimethylation. Intriguingly, the silencing domain is also required to target the episomal vector to the perinucleolar compartment during mid-S phase. Collectively, our data unfold a novel mechanism by which an antisense RNA mediates transcriptional gene silencing of chromosomal domains by targeting them to distinct nuclear compartments known to be rich in heterochromatic machinery.
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