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Originally published in Science Express on 6 November 2008
Science 12 December 2008:
Vol. 322. no. 5908, pp. 1717 - 1720
DOI: 10.1126/science.1163802
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Reports

The Air Noncoding RNA Epigenetically Silences Transcription by Targeting G9a to Chromatin

Takashi Nagano,1,2* Jennifer A. Mitchell,1 Lionel A. Sanz,3 Florian M. Pauler,4 Anne C. Ferguson-Smith,5 Robert Feil,3 Peter Fraser1*

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.

1 Laboratory of Chromatin and Gene Expression, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
2 Division of Cell Biology and Neuroscience, Department of Morphological and Physiological Sciences, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan.
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, and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.

* To whom correspondence should be addressed. E-mail: takashi.nagano{at}bbsrc.ac.uk (T.N.); peter.fraser{at}bbsrc.ac.uk (P.F.)

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