This Article Full Text (PDF) Other Versions of this Article: MCB.02263-07v1 28/11/3713    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Mohammad, F. Articles by Kanduri, C. Search for Related Content PubMed PubMed Citation Articles by Mohammad, F. Articles by Kanduri, C.

 Previous Article  |  Next Article 

Mol. Cell. Biol. doi:10.1128/MCB.02263-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Kcnq1ot1/Lit1 noncoding RNA mediates transcriptional silencing by targeting to the perinucleolar region

Department of Genetics and Pathology, Dag Hammarskölds Väg 20, 75185 Rudbeck Laboratory, Uppsala University, Uppsala, Sweden; Department of Genetics and Development, Norbyvägen18A, S-75236, Uppsala University, Uppsala, Sweden; Laboratory of Chromatin and Gene Expression, Babraham Institute, Babraham Research Campus, Cambridge, CB2243AT, United Kingdom

^* To whom correspondence should be addressed. Email: Kanduri.Chandrasekhar{at}genpat.uu.se.

	Abstract

The Kcnq1ot1 antisense non-coding 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 lysine9-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.