Project description:Hepatocellular carcinomas (HCC) exhibit distinct promoter hypermethylation patterns, but the epigenetic regulation and function of transcriptional enhancers remain unclear. Here, our affinity- and bisulfite-based whole-genome sequencing analyses reveal global enhancer hypomethylation in human HCCs. Integrative epigenomic characterization further pinpoints a recurrent hypomethylated enhancer of CCAAT/enhancer-binding protein-beta (C/EBPβ) which correlates with C/EBPβ over-expression and poorer prognosis of patients. Demethylation of C/EBPβ enhancer reactivates a self-reinforcing enhancer-target loop via direct transcriptional up-regulation of enhancer RNA. Conversely, deletion of this enhancer via CRISPR/Cas9 reduces C/EBPβ expression and its genome-wide co-occupancy with BRD4 at H3K27ac-marked enhancers and super-enhancers, leading to drastic suppression of driver oncogenes and abrogation of HCC tumorigenicity. Hepatitis B X protein transgenic mouse model of HCC recapitulates this paradigm, as C/ebpβ enhancer hypomethylation associates with oncogenic activation in early tumorigenesis. These results support a causal link between aberrant enhancer hypomethylation and C/EBPβ over-expression, thereby driving hepatocarcinogenesis through global transcriptional reprogramming.

2019-01-06 | GSE123097 | GEO

Aberrant enhancer reprogramming drives hepatic carcinogenesis through global transcriptional reprogramming [RNA-seq]

2019-01-06 | GSE123098 | GEO

Aberrant enhancer reprogramming drives hepatic carcinogenesis through global transcriptional reprogramming

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-01-06 | GSE123099 | GEO

Aberrant enhancer hypomethylation contributes to hepatic carcinogenesis through global transcriptional reprogramming.

Project description: Not available

| S-EPMC6338783 | biostudies-literature

Loss of tumor suppressor IGFBP4 drives epigenetic reprogramming in hepatic carcinogenesis.

Project description: Not available

| S-EPMC6158508 | biostudies-literature

Hepatic expression data from 2-stage carcinogenesis study in rats

Project description:Hepatic gene expression profiles in 2-stage carcinogenesis study were analyzed with comprehensive DNA methylation data. Combined analysis suggested that PTEN signaling and immune response such as antigen presentation was related to one side of early heapatocarcinogenesis. We used microarrays to obtain the global gene expression profile of livers to understand the mechanism of carcinogenesis.

2016-10-24 | GSE51797 | GEO

Transcription profiling of rodent hepatic carcinogenesis

Project description:3 dose levels of each of 9 compounds were used to dose male SD rats q.d. by oral gavage. Compounds included 5 nongenotoxic carcinogens (bemitradine, clofibrate, doxylamine, methapyrilene, & phenobarbital), 2 genotoxic agents (tamoxifen and 2-AAF) and 2 non-carcinogens (4-AAF and isoniazid). This work has been described in Kramer JA, Curtiss SW, Kolaja KL, Alden CA, Blomme EAG, Curtiss WC, Davila JC, Jackson CJ, and Bunch RT. (2004) Acute Molecular Markers of Rodent Hepatic Carcinogenesis Identified by Transcription Profiling. Chem. Res. Toxicol., in press.

2004-03-08 | E-MEXP-89 | biostudies-arrayexpress

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