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| Status |
Public on Jul 02, 2018 |
| Title |
Epigenetic reprogramming in hepatic carcinogenesis |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Genomic sequencing of hepatocellular carcinoma (HCC) uncovers a paucity of actionable mutations, underscoring the necessity to exploit epigenetic vulnerabilities for therapeutics. In HCC, EZH2-mediated H3K27me3 represents a major oncogenic chromatin modification, but how it modulates the therapeutic vulnerability of signaling pathways remains unknown. Here, we identified that EZH2 maintains H3K27 methylome through epigenetic silencing of specific gene sets. ChIP-seq revealed enrichment of EZH2/H3K27me3 at silenced loci in HBx-transgenic (TG) mouse-derived HCCs, including tumor suppressors whose down-regulation significantly correlated with EZH2 overexpression and poor survival of HCC patients. Defining the aberrant chromatin landscape of HCC sheds light into the mechanistic basis of effective EZH2-targeted inhibition.
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| Overall design |
The normal liver (NL) tissue from 3 month-old wild-type (WT) C57BL/6 mouse, and the non-tumor (NT) and tumor (T) tissues from 18 month-old HBx-TG mice were collected for ChIP-seq analyses using antibodies targeting EZH2 and H3K27me3. The genome-wide enrichment of EZH2 and H3K27me3 in T tissue was compared against those in NL and NT tissues, respectively, as to identify the epigenentically silenced gene sets unique to HCCs.
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| |
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| Contributor(s) |
Lee Y, Mok MT, Wu F, Cheng AS |
| Citation(s) |
29992318 |
| |
| Submission date |
Apr 18, 2018 |
| Last update date |
Oct 03, 2018 |
| Contact name |
Alfred Sze-Lok Cheng |
| E-mail(s) |
[email protected]
|
| Organization name |
The Chinese University of Hong Kong
|
| Department |
School of Biomedical Sciences
|
| Street address |
Rm 405A, Lo Kwee-Seong Integrated Biomedical Sciences Building, Area 39, CUHK
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| City |
Hong Kong |
| ZIP/Postal code |
0000 |
| Country |
Hong Kong |
| |
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| Platforms (1) |
| GPL18480 |
Illumina HiSeq 1500 (Mus musculus) |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA450821 |
| SRA |
SRP140915 |
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