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| Status |
Public on May 17, 2016 |
| Title |
Chromatin IP for H3 K27me3 modified histone tails in the liver of control mice, Phenobarbital exposed mice and a resulting Ctnnb1 mutated PB liver tumour [ChIP-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| 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.
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| Overall design |
We carry out Chromatin immunoprecipitation (ChIP) prior to sequencing on Illumina Hiseq 2500 to report on the genome-wide H3K27me3 patterns in normal mouse liver, 12 week Phenobarbital exposed mouse livers and 35 week pehonbarbital exposed liver tumours.
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| Contributor(s) |
Thomson JP, Meehan RR |
| 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
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| Lab |
Meehan
|
| Street address |
Crewe Road
|
| City |
Edinburgh |
| ZIP/Postal code |
EH4 2XU |
| Country |
United Kingdom |
| |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (4)
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| 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 |
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| Relations |
| BioProject |
PRJNA311320 |
| SRA |
SRP069818 |
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