Paupar long non-coding RNA promotes KAP1 dependent chromatin changes and regulates olfactory bulb neurogenesis [gene expression]

These data show that Paupar, a CNS expressed long non-coding RNA (lncRNA), directly and functionally associates with KAP1, an essential epigenetic regulatory protein. Transcriptome profiling of N2A cells identified 1,913 differentially expressed genes whose expression significantly changed (at a 5% false discovery rate [FDR]) greater than 1.4-fold (log2 fold change 0.5) upon KAP1 depletion. Examination of the intersection of KAP1 and Paupar transcriptional targets showed that Paupar and KAP1 control expression of a shared set of target genes that are enriched for regulators of neuronal function and cell cycle in N2A cells. Furthermore, CHART-seq and ChIP-seq derived Paupar-KAP1 genome-wide co-occupancy maps revealed a 4-fold enrichment of overlap between Paupar and KAP1 bound sequences on chromatin. This study also indicates that Paupar promotes KAP1 chromatin occupancy and H3K9me3 deposition at a subset of distal targets, through formation of a ribonucleoprotein complex containing Paupar, KAP1 and the PAX6 transcription factor. These observations provide important conceptual insights into the trans-acting modes of lncRNA-mediated epigenetic regulation and the mechanisms of KAP1 genomic recruitment.

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Pavlaki I, Alammari F, Sun B, Clark N, Sirey T, Lee S, Woodcock DJ, Ponting CP, Szele FG, Vance KW