The long non‐coding RNA P aupar regulates the expression of both local and distal genes

Although some long noncoding RNA s (lnc RNA s) have been shown to regulate gene expression in cis , it remains unclear whether lnc RNA s can directly regulate transcription in trans by interacting with chromatin genome‐wide independently of their sites of synthesis. Here, we describe the genomically local and more distal functions of Paupar , a vertebrate‐conserved and central nervous system‐expressed lnc RNA transcribed from a locus upstream of the gene encoding the PAX 6 transcription factor. Knockdown of P aupar disrupts the normal cell cycle profile of neuroblastoma cells and induces neural differentiation. Paupar acts in a transcript‐dependent manner both locally, to regulate Pax6 , as well as distally by binding and regulating genes on multiple chromosomes, in part through physical association with PAX 6 protein. Paupar binding sites are enriched near promoters and can function as transcriptional regulatory elements whose activity is modulated by P aupar transcript levels. Our findings demonstrate that a lnc RNA can function in trans at transcriptional regulatory elements distinct from its site of synthesis to control large‐scale transcriptional programmes.