Super-enhancer driven MYST family histone lysine acetyltransferases are critical for nasopharyngeal carcinoma cell growth and survival

Nasopharyngeal carcinoma (NPC) is causally linked to Epstein-Barr virus (EBV) infection, genetic predisposition and environmental factors. Early diagnosis is difficult due to lack of specific symptoms. Many patients have advanced disease at diagnosis and these patients respond to treatment poorly. To better understand the NPC molecular pathogenesis, genome-wide CRISPR screen was used to identify NPC dependency factors. These dependency factors were then linked to their enhancers using H3K27ac HiChIP. The screen identified MYST histone acetyl transferase complex, NF-kB signaling pathway, purine synthesis pathway, linear ubiquitination pathway, SLC2A1, MDM2, and PIK3C3 as NPC dependency factors/pathways. Importantly, H3K27ac HiChIP linked most of these dependency factors to super-enhancers. This study provided new insight to NPC pathogenesis and also identified novel potential targets for therapy. CRISPR screens and H3K27ac HiChIP were performed in EBV positive NPC cell lines (C666-1, C17) as well as the EBV negative NPC cell line (NP69)