title: Kcnq1ot1/Lit1 noncoding RNA mediates transcriptional silencing by targeting to the perinucleolar region.
abstract: 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.
authors.affiliation: Uppsala University, Department of Genetics and Pathology, Rudbeck Laboratory, Dag Hammarskölds Väg 20, 75185 Uppsala, Sweden.
authors.forename: Faizaan
authors.initials: F
authors.lastname: Mohammad
authors.forename: Radha Raman
authors.initials: RR
authors.lastname: Pandey
authors.forename: Takashi
authors.initials: T
authors.lastname: Nagano
authors.forename: Lyubomira
authors.initials: L
authors.lastname: Chakalova
authors.forename: Tanmoy
authors.initials: T
authors.lastname: Mondal
authors.forename: Peter
authors.initials: P
authors.lastname: Fraser
authors.forename: Chandrasekhar
authors.initials: C
authors.lastname: Kanduri
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D002466:Cell Nucleolus / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D017124:Conserved Sequence; D020868:Gene Silencing; D017930:Genes, Reporter; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D010957:Plasmids / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D011401:Promoter Regions, Genetic; D016372:RNA, Antisense / Q000235:genetics / Q000378:metabolism*; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; C485621:KCNQ1OT1 long non-coding RNA, human; D008565:Membrane Proteins; D024642:Potassium Channels, Voltage-Gated; D016372:RNA, Antisense; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C077885:XIST non-coding RNA