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Series GSE77725 Query DataSets for GSE77725
Status Public on May 17, 2016
Title IP of 5-methylcytosine (5-mc) enriched DNA fragments from control and mice with non-acoholic steatohepatitis (NASH) related hepatocellular carcinoma (HCC)
Organism Mus musculus
Experiment type Methylation profiling by genome tiling array
Summary Through the analysis of mouse liver tumours promoted by distinct routes (DEN exposure alone, DEN exposure plus non-genotoxic insult with phenobarbital and non-alcoholic fatty liver disease); we report that the cancer associated hyper-methylated CGI events in mice are also predicated by silent promoters that are enriched for both the DNA modification 5-hydroxymethylcytosine (5hmC) and the histone modification H3K27me3 in normal liver. During cancer progression these CGIs undergo hypo-hydroxymethylation, prior to subsequent hyper-methylation; whilst retaining H3K27me3. A similar loss of promoter-core 5hmC is observed in Tet1 deficient mouse livers indicating that reduced Tet1 binding at CGIs may be responsible for the epigenetic dysregulation observed during hepatocarcinogenesis. Consistent with this reduced Tet1 protein levels are observed in mouse liver tumour lesions. As in human, DNA methylation changes at CGIs do not appear to be direct drivers of hepatocellular carcinoma progression in mice. Instead dynamic changes in H3K27me3 promoter deposition are strongly associated with tumour-specific activation and repression of transcription. Our data suggests that loss of promoter associated 5hmC in diverse liver tumours licences DNA methylation reprogramming at silent CGIs during cancer progression.
 
Overall design 5-mc is a well establisehd epigenetic mark typically related to gene silencing events. Phenobarbital (PB) is a well studied non-genotoxic carcinogen with roles in epigenetic perturbation. We profile 5mC in both control mouse livers as well as in liver tumours of high fat diet exposed mice who have progressed through NASH. Samples: 5mC profiles in livers of 2 control and 2 NASH driven HCC samples
 
Contributor(s) Thomson JP, Ottaviano R, Meehan R
Citation(s) 27197233
Submission date Feb 09, 2016
Last update date Dec 12, 2019
Contact name John Paterson Thomson
E-mail(s) john.thomson@igmm.ed.ac.uk
Organization name University of Edinburgh
Department MRC Human Genetics Unit
Lab Meehan
Street address Crewe Road
City Edinburgh
ZIP/Postal code EH4 2XU
Country United Kingdom
 
Platforms (1)
GPL16743 Agilent-028383 SurePrint G3 Mouse Promoter Microarray 1x1M
Samples (8)
GSM2057933 control mouse 1 5mC profile
GSM2057934 control mouse 2 5mC profile
GSM2057935 NASH driven tumour mouse 1 5mC profile
This SubSeries is part of SuperSeries:
GSE77731 Profiling of epigenetic and transcriptomic landscapes in normal mouse liver, phenobarbital exposed mouse livers and mouse liver tumours
Relations
BioProject PRJNA311318

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE77725_MeDIP_NASH_study.txt.gz 42.4 Mb (ftp)(http) TXT
GSE77725_RAW.tar 813.4 Mb (http)(custom) TAR (of TXT)
GSE77725_hmeDIP_NASH_study.txt.gz 42.2 Mb (ftp)(http) TXT
Processed data are available on Series record

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