While the mammalian genome encodes thousands of lincRNA genes, few have been functionally characterized. We performed an unbiased loss-of-function analysis of lincRNAs expressed in ESCs and show that lincRNAs are clearly functional and primarily act in trans to affect global gene expression. We establish that lincRNAs are key components of the ESC transcriptional network that are functionally important for maintaining the pluripotent state, and that many are down-regulated upon differentiation. The ESC lincRNAs physically interact with chromatin proteins, many of which have been previously implicated in the maintenance of the pluripotent state18,20,21. In addition to chromatin proteins, lincRNAs interact with other protein complexes including many RNA-binding proteins (data not shown).
