Submitted on July 25, 2008
Accepted on October 28, 2008
The Air Noncoding RNA Epigenetically Silences Transcription by Targeting G9a to Chromatin
Takashi Nagano 1, Jennifer A. Mitchell 2, Lionel A. Sanz 3, Florian M. Pauler 4, Anne C. Ferguson-Smith 5, Robert Feil 3, Peter Fraser 2*
1 Laboratory of Chromatin and Gene Expression, The Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, United Kingdom.; Division of Cell Biology and Neuroscience, Department of Morphological and Physiological Sciences, Faculty of Medical Sciences, University of Fukui, Fukui, 910-1193, Japan.
2 Laboratory of Chromatin and Gene Expression, The Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, United Kingdom.
3 Institute of Molecular Genetics, CNRS UMR-5535 and University of Montpellier-II, 34293 Montpellier, France.
4 CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, c/o Vienna Biocenter, Dr Bohr-Gasse 9/4, 1030 Vienna, Austria.
5 Department of Physiology, Development & Neuroscience, University of Cambridge, Cambridge, CB2 3EG, United Kingdom.
* To whom correspondence should be addressed.
Peter Fraser , E-mail: peter.fraser{at}bbsrc.ac.uk
A number of large noncoding RNAs (ncRNA) 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 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 bi-allelic 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.
