title: The Air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin.
abstract: A number of large noncoding RNAs (ncRNAs) epigenetically silence genes through unknown mechanisms. The Air ncRNA is imprinted--monoallelically expressed from the paternal allele. Air is required for allele-specific silencing of the cis-linked Slc22a3, Slc22a2, and Igf2r genes in mouse placenta. We show that Air interacts with the Slc22a3 promoter chromatin and the H3K9 histone methyltransferase G9a in placenta. Air accumulates at the Slc22a3 promoter in correlation with localized H3K9 methylation and transcriptional repression. Genetic ablation of G9a results in nonimprinted, biallelic transcription of Slc22a3. Truncated Air fails to accumulate at the Slc22a3 promoter, which results in reduced G9a recruitment and biallelic transcription. Our results suggest that Air, and potentially other large ncRNAs, target repressive histone-modifying activities through molecular interaction with specific chromatin domains to epigenetically silence transcription.
authors.affiliation: Laboratory of Chromatin and Gene Expression, Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK. takashi.nagano@bbsrc.ac.uk
authors.forename: Takashi
authors.initials: T
authors.lastname: Nagano
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Mitchell
authors.forename: Lionel A
authors.initials: LA
authors.lastname: Sanz
authors.forename: Florian M
authors.initials: FM
authors.lastname: Pauler
authors.forename: Anne C
authors.initials: AC
authors.lastname: Ferguson-Smith
authors.forename: Robert
authors.initials: R
authors.lastname: Feil
authors.forename: Peter
authors.initials: P
authors.lastname: Fraser
mesh_terms: D000483:Alleles; D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005260:Female; D018392:Genomic Imprinting; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008745:Methylation; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D022661:RNA, Untranslated / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D000099254:Organic Cation Transporter 3
chemical_list: D002843:Chromatin; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones; D027701:Organic Cation Transport Proteins; D022661:RNA, Untranslated; D000099254:Organic Cation Transporter 3; C533711:G9a protein, mouse