HOXC9-induced neuronal differentiation in human neuroblastoma BE(2)-C cells [ChIP-seq analysis]

Cell differentiation is an essential process of normal development by which a stem cell or progenitor cell becomes a post-mitotic, specialized cell with unique morphology and function. Also, it has long been recognized that differentiation is associated with a marked reduction in DNA damage response at the global level. The molecular basis for the coordination between cell cycle exit, acquirement of specialized structure and function, and attenuation of DNA damage response during differentiation is not well understood. We have conducted a genome-wide analysis of the HOXC9-induced neuronal differentiation program in human neuroblastoma cells. Gene expression profiling reveals that HOXC9-induced differentiation is associated with transcriptional regulation of 2,395 genes, which is characterized by global upregulation of neuronal genes and downregulation of cell cycle and DNA repair genes. Remarkably, genome-wide mapping demonstrates that HOXC9 occupies 40% of these genes, including a large number of genes involved in neuronal differentiation, cell cycle progression and DNA damage response. These findings suggest that HOXC9 directly activates and represses the transcription of distinct sets of genes to coordinate the cellular events characteristic of neuronal differentiation.