Analysis of Chromatin Accessibility Landscapes in Esophageal Squamous Cell Carcinoma

Abstract

Esophageal cancer ranks sixth among all cancers in mortality and is associated with malfunction in gene regulation and expression. Assay for Transposase‐Accessible Chromatin with high‐throughput sequencing (ATAC‐seq) can reveal the locations of regulatory elements across the genome and discover the mechanisms of chromatin structure that govern gene expression programs. This study compared the chromatin accessibility landscapes between esophageal squamous cell carcinoma cell lines (ESCC), i.e. KYSE‐30 and KYSE‐150, and non‐cancerous esophageal epithelial cell lines (NC), i.e. HET‐1A and NES‐G4T. Opened and closed chromatin regions were associated to the nearest genes, and gene ontology analyses (GO) were performed. The results demonstrated that many regions were more accessible in ESCC cells than in NC cells. These regions belong to the GO terms including positive regulation of GTPase activity, metabolic process, and nucleosome assembly. Furthermore, the promoter‐proximal peaks at genome‐wide scale predicted that several genes in histone gene cluster 1 on chromosome 6p22 were transcriptionally active in ESCC cells. To confirm that the promoter region with enhanced accessibility indeed is indicative to gene expression, the mRNA level of a few representative genes were examined. For example, the expression of PLCB1 gene, which encodes phospholipase C beta 1, a key regulator for GTPase activity and MAPK signaling, was confirmed to be up‐regulated in both ESCC cells. There were also some regions more inaccessible in ESCC cells than in NC cells and they belonged to different GO terms, chiefly associated with cellular homeostasis. This study may aid to reveal the instrumental epigenetic changes responsible for differential gene expression and ESCC development.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.