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.
The Air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin
Nagano, T.; Mitchell, J. A.; Sanz, L. A.; Pauler, F. M.; Ferguson-Smith, A. C.; Feil, R.; Fraser, P.
2008-12-12 / vol 322 / pages 1717-20
1163802 [pii] 10.1126/science.1163802
1095-9203 (Electronic) 0036-8075 (Linking)
IGMM team(s) involved in this publication
Genomic Imprinting and Development
Female; Animals; Mice; *Transcription, Genetic; Histones/metabolism; Male; *RNA Interference; Alleles; Epigenesis, Genetic; Genomic Imprinting; Methylation; Promoter Regions, Genetic; RNA, Untranslated/*genetics/metabolism; Pregnancy; In Situ Hybridization, Fluorescence; Chromatin/*metabolism; Mice, Inbred BALB C; Histone-Lysine N-Methyltransferase/*metabolism; Myocardium/metabolism; Organic Cation Transport Proteins/*genetics; Placenta/*metabolism