The long non-coding RNA promotes KAP1-dependent chromatin changes and regulates olfactory bulb neurogenesis.

Many long non-coding RNAs (lncRNAs) are expressed during central nervous system (CNS) development, yet their roles and mechanisms of action remain poorly understood. , a CNS-expressed lncRNA, controls neuroblastoma cell growth by binding and modulating the activity of transcriptional regulatory elements in a genome-wide manner. We show here that the lncRNA directly binds KAP1, an essential epigenetic regulatory protein, and thereby regulates the expression of shared target genes important for proliferation and neuronal differentiation. promotes KAP1 chromatin occupancy and H3K9me3 deposition at a subset of distal targets, through the formation of a ribonucleoprotein complex containing , KAP1 and the PAX6 transcription factor. -KAP1 genome-wide co-occupancy reveals a fourfold enrichment of overlap between and KAP1 bound sequences, the majority of which also appear to associate with PAX6. Furthermore, both and loss-of-function disrupt olfactory bulb neurogenesis. These observations provide important conceptual insights into the -acting modes of lncRNA-mediated epigenetic regulation and the mechanisms of KAP1 genomic recruitment, and identify and as regulators of neurogenesis .