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Many intergenic long noncoding RNA (lncRNA) loci regulate the expression of adjacent protein coding genes. Less clear is whether intergenic lncRNAs commonly regulate transcription by modulating chromatin at genomically distant loci. Here, we report both genomically local and distal RNA-dependent roles of  Dali , a conserved central nervous system expressed intergenic lncRNA.  Dali  is transcribed downstream of the  Pou3f3  transcription factor gene and its depletion disrupts the differentiation of neuroblastoma cells. Locally,  Dali  transcript regulates transcription of the  Pou3f3  locus. Distally, it preferentially targets active promoters and regulates expression of neural differentiation genes, in part through physical association with the POU3F3 protein.  Dali  interacts with the DNMT1 DNA methyltransferase in mouse and human and regulates DNA methylation status of CpG island-associated promoters in  trans . These results demonstrate, for the first time, that a single intergenic lncRNA controls the activity and methylation of genomically distal regulatory elements to modulate large-scale transcriptional programmes.

The long non-coding RNA Dali is an epigenetic regulator of neural differentiation