Open AccessMaster transcription factors form interconnected circuitry and orchestrate transcriptional networks in oesophageal adenocarcinoma
Author(s) -
Li Chen,
Moli Huang,
Jasmine Plummer,
Jian Pan,
Yan Jiang,
Qian Yang,
Tiago C. Silva,
Nicole Gull,
Stephanie Chen,
Ling-Wen Ding,
Ömer An,
Henry Yang,
Yulan Cheng,
Jonathan Said,
Ngan Doan,
Winand N.M. Dinjens,
Kevin M. Waters,
Richard Tuli,
Simon A. Gayther,
Samuel J. Klempner,
Benjamin P. Berman,
Stephen J. Meltzer,
De Lin,
H. Phillip Koeffler
Publication year - 2019
Publication title -
gut
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.413
H-Index - 293
eISSN - 1468-3288
pISSN - 0017-5749
DOI - 10.1136/gutjnl-2019-318325
Subject(s) - enhancer , transcription factor , chromatin immunoprecipitation , biology , epigenome , gata6 , chromatin , transcriptome , cancer research , transcriptional regulation , computational biology , gene , genetics , microbiology and biotechnology , gene expression , dna methylation , promoter
While oesophageal squamous cell carcinoma remains infrequent in Western populations, the incidence of oesophageal adenocarcinoma (EAC) has increased sixfold to eightfold over the past four decades. We aimed to characterise oesophageal cancer-specific and subtypes-specific gene regulation patterns and their upstream transcription factors (TFs). DESIGN: To identify regulatory elements, we profiled fresh-frozen oesophageal normal samples, tumours and cell lines with chromatin immunoprecipitation sequencing (ChIP-Seq). Mathematical modelling was performed to establish (super)-enhancers landscapes and interconnected transcriptional circuitry formed by master TFs. Coregulation and cooperation between master TFs were investigated by ChIP-Seq, circularised chromosome conformation capture sequencing and luciferase assay. Biological functions of candidate factors were evaluated both in vitro and in vivo.