Interplay between H2A.Z and epigenome in PANC-1. Interplay between H2A.Z and epigenome in PANC-1

The oncogenic process is regulated by a complex network of different regulatory elements in charge of regulate the cancer epigenome. The histone variant H2A.Z is involved in the regulation of different regulatory elements such as promoters and enhancers in different types of cancer, however, the interplay between the H2A.Z and the cancer epigenome is poorly understood. Here, we investigate the functional role of H2A.Z at promoters, enhancers, super enhancers and topologically associating domains in the pancreatic cancer cell line PANC-1. We found an oncogenic role of H2A.Z regulated by acetylation and deacetylation as well as the potential interactions with epigenetic regulators such as EZH2 and CTCF. Specifically, we found that the presence of H2A.Z facilitates the recruitment of RNA polymerase II and other transcription factors such as ZNF384 at promoters, enhancers and super enhancers, allowing the gene expression. On the other hand, the absence of acetylation is associated with an enrichment of EZH2 allowing transcriptional repression of transcription factors associated with cancer development. Also, we identified that H2A.Z is a component of the TAD boundaries in PANC-1, and its enrichment is associated with the presence of transcription factors such as CTCF, ZNF143 and ZNF384. Together, these data show new mechanisms associated with the interplay between H2A.Z and the epigenome in pancreatic cancer. Overall design: ChIP-seq of H2A.Z and acH2A.Z in the pancreatic cancer cell line PANC-1, and RNA-seq from H2A.Z knock-down clone named PZT-1 generated with shRNA in the PANC-1