The mammalian genome encodes many thousands of large non-coding transcripts1 including a class of ~3500 large intergenic ncRNAs (lincRNAs) identified using a chromatin signature of actively transcribed genes2–4. These lincRNA genes have been shown to have interesting properties, including clear evolutionary conservation2–5, expression patterns correlated with various cellular processes2,6 and binding of key transcription factors to their promoters2,6, and the lincRNAs themselves physically associate with chromatin regulatory proteins4,7. Yet, it remains unclear whether the RNA transcripts themselves have biological functions8–10. Few have been demonstrated to have phenotypic consequences by loss-of-function experiments6. As a result, the functional role of lincRNA genes has been widely debated. Various proposals include that lincRNA genes act as enhancer regions, with the RNA transcript simply being an incidental by-product8,9, that lincRNA transcripts act in cis to activate transcription11, and that lincRNA transcripts can act in trans to repress transcription12,13.
