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Series GSE77727 Query DataSets for GSE77727
Status Public on May 17, 2016
Title IP of 5-methylcytosine (5-mc) enriched DNA fragments from control, PB treated mouse livers, resulting Ctnnb1 mutated PB liver tumours and PB minus Ha-Ras mutate liver tumour
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 the livers of 12 week PB treated mice. We also profile 5mC in liver tumours arising in the presence of long term PB exposure (35 week: resulting in Ctnnb1 mutated tumours) to a Ha-Ras liver tumour which arose without PB. Samples: 2 control and 2 PB exposed mouse livers, 3 liver tumours resulting from long term PB exposrue and 1 liver tumour arising without PB
Contributor(s) Thomson JP, LempiƤinen H, Muller A, Terranova R, Moggs JG, Schwarz M, Meehan R
Citation(s) 27197233
Submission date Feb 09, 2016
Last update date Dec 12, 2019
Contact name John Paterson Thomson
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 (2)
GPL14890 NimbleGen Mouse 2.1M deluxe promoter array [100205_MM9_Promoter_MeDIP_HX1]
GPL17878 NimbleGen Mouse MM9 Deluxe Promoter Array (100718_MM9_Promoter_MeDIP_HX1)
Samples (8)
GSM2057949 control mouse 1 5mC profile
GSM2057950 control mouse 2 5mC profile
GSM2057951 pb treated 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
BioProject PRJNA311321

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
GSE77727_5mC_data_processed.txt.gz 119.2 Mb (ftp)(http) TXT
GSE77727_RAW.tar 918.2 Mb (http)(custom) TAR (of PAIR)
Processed data are available on Series record

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