Journal
MAMMALIAN GENOME
Volume 20, Issue 9-10, Pages 557-562Publisher
SPRINGER
DOI: 10.1007/s00335-009-9218-1
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Funding
- BBSRC [BB/D014050/1, BBS/E/B/0000C151] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BBS/E/B/0000C151, BB/D014050/1] Funding Source: Medline
- Biotechnology and Biological Sciences Research Council [BBS/E/B/0000C151, BB/D014050/1] Funding Source: researchfish
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Long noncoding RNAs (lncRNAs) such as Xist, Air, and Kcnq1ot1 are required for epigenetic silencing of multiple genes in cis within large chromosomal domains, including distant genes located hundreds of kilobase pairs away. Recent evidence suggests that all three of these lncRNAs are functional and that they silence gene expression, in part, through an intimate interaction with chromatin. Here we provide an overview of lncRNA-dependent gene silencing, focusing on recent findings for the Air and Kcnq1ot1 lncRNAs. We review molecular evidence indicating that these lncRNAs interact with chromatin and correlate their presence with specific histone modifications associated with gene silencing. A general model for a lncRNA-dependent gene-silencing mechanism is presented based on the apparent ability of lncRNAs to recruit histone-modifying activities to chromatin. However, alternate mechanisms may be required to explain the silencing of some lncRNA-dependent genes. Finally, we discuss unanswered questions and future perspectives associated with these enigmatic lncRNA molecules.
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