Genome-wide occupancy of ZRF1 and BRD4 in neuroblastoma cells.

Neuroblastoma (NB), a malignant embryonic tumor arising from primitive neural crest cells, accounts for more than 7% of malignancies and around 15% of cancer-related mortality in childhood. Better elucidating the mechanisms of tumorigenesis and aggressiveness is important for improving the therapeutic efficiencies of NB. Through integrated proteomics and validating studies, we discovered that ZRF1 and BRD4 form a complex with p113, a novel protein derived from CUX1 circular RNA. To investigate the mechanisms underlying the oncogenic functions of ZRF1 and BRD4, we employed the Illumina Novaseq 6000 as a discovery platform to analyze the genome-wide occupancy of ZRF1 and BRD4 on target genes in human SH-SY5Y cells, while the results were further analyzed with p113-regulated target genes. The results showed that 46 target genes were regulated by transcriptional trimer complex p113/ZRF1/BRD4, especially those involved in metabolic pathway or complex I biogenesis, including ALDH3A1, NDUFA1, and NDUFAF5. Furthermore, we validated the ChIP-seq results by real-time PCR with high identity. Overall, our results provided fundamental information about the genomic enrichment of ZRF1 and BRD4 in human NB cells, and these findings will help us understand the pathogenesis of NB. Examination of genome-wide occupancy of two different transcriptional regulators in neuroblastoma cells.