Identifying super enhancer-associated master transcription factors in primary human hepatocellular carcinoma
Refereed conference paper presented and published in conference proceedings


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AbstractHepatocellular carcinoma (HCC) has become a prominent global health threat due to its occurrence, lethality and low 5-year patient survival rates. Increasing prevalence of obesity and diabetes-induced non-alcoholic fatty liver disease (NAFLD) and metabolic syndromes have been found culpable for the rise of HCC initiation, via disruption of liver microenvironment.1 Super enhancers, which are characterized by high density of transcription binding sites, high-level transcription regulation and response to external stimulation, determine cell fate during oncogenesis.2 Master transcription factors translate microenvironmental changes into super enhancer remodelling and activation, which subsequently changes the gene expression profile and define cell identity.3 This project aims at profiling the super enhancer status in the context of NAFLD-associated HCC and to unveil the master transcription factors responsible for diet-induced HCC progression. Nanoscale chromatin immunoprecipitation sequencing (nano ChIP-seq) against histone marks H3K27ac, H3K4me1 and H3K4me3 in 6 pairs of primary human NAFLD-HCC tumours and their adjacent non-tumour tissues revealed potential oncogenic super enhancers (averaged 553 and 484 per HCC tumor and non-tumor tissues, respectively). Global mRNA expression was detected by RNA sequencing (RNA-seq) to support the enhancer-target gene transcription axis. Tumour-enabling super enhancers were profiled in primary human NAFLD-HCC tissues and master transcription factors were identified using integrated bioinformatic analysis, including motif enrichment analysis and signature transcription factor discovery. ChIP-seq data for the master transcription factors in HepG2 cells confirmed their occupancies on super enhancers controlling key oncogenic pathways. Interestingly, tumour-enabling super enhancers co-bound by HCC-specific master transcription factors target critical genes involved in hepatic inflammation and NAFLD pathogenesis. Integrated analysis of chromatin profiling and transcriptome in primary human tissues provides insights in the trans-regulatory network of metabolic syndrome-associated HCC pathogenesis.
All Author(s) ListOtto K. CHEUNG, Feng WU, Patrick TAN, Kevin Y. YIP, Alfred S. CHENG
Name of ConferenceThe Cold Spring Harbor Asia conference on Chromatin, Epigenetics & Transcription
Start Date of Conference16/04/2018
End Date of Conference20/04/2018
Place of ConferenceSuzhou
Country/Region of ConferenceChina
Year2018
Month4
Day16
LanguagesEnglish-United States

Last updated on 2018-11-10 at 17:32