Large Intergenic Non‐Coding RNAs in Chromatin, Cancer and Stem Cells

We recently discovered a new class of highly conserved large intergenic non‐coding RNAs (lincRNAs) and a computational method to predict their functions. This “guilt by association method” pointed to a clear association of lincRNAs with chromatin remodeling complexes, particularly in the context of cancer and pluripotent cell states. Here, we present a systematic and comprehensive approach that demonstrates a majority of lincRNAs associate with various chromatin‐remodeling complexes and regulate specific genomic sites in cancer and the derivation of induced pluripotent stem cells. As one example, we show that p53 directly and temporally induces several lincRNAs in response to DNA damage. Including lincRNA‐p21 that is required for proper localization of chromatin factors to mediate p53 dependent cellular apoptosis. Together, these results point to key regulatory roles for lincRNAs across diverse biological pathways, through interfacing with and imparting specificity to chromatin modifying remodeling complexes.