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| Status |
Public on Aug 12, 2009 |
| Title |
Combinatorial pharmacological approaches target EZH2-mediated gene repression in breast cancer cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Polycomb protein EZH2-mediated gene silencing is implicated in breast tumorigenesis through methylation of histone H3 on Lysine 27 (H3K27). We have previously shown that S-adenosylhomocysteine hydrolase (SAHH) inhibitor 3-Deazaneplanocin A (DZNep) can modulate histone methylation and disrupt EZH2 complex. Here, we used DZNep, together with other chromatin remodeling agents, as well as RNA interference-mediated EZH2 depletion, to probe the role of EZH2 in coordination with other epigenetic components in gene regulation in breast cancer cells. Through genome-wide gene expression analysis, coupled with extensive chromatin immunoprecipitation analysis of histone modifications, we have identified a variety of gene sets that are regulated either by EZH2 alone or through the coordinated action of EZH2 with HDAC and/or DNA methylation. We further found that tumor antigen GAGEs were regulated by distinct epigenetic mechanisms in a cell context-dependent manner, possibly reflecting mechanistic heterogeneity in breast cancer. Intriguingly, we found that EZH2 regulates a remarkable cohort of genes whose functions are highly enriched in immunoresponse and autocrine inflammation network, and their transcriptional activation upon EZH2 perturbation is cancer-specific, revealing a potential novel role of EZH2 in regulating cancer immunity. These findings demonstrate the complexity and diversity of epigenetic regulation in human cancer and underscore the importance for developing combinatorial pharmacologic approaches for effective epigenetic gene reactivation.
Keywords: Total RNA
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| Overall design |
Cells were treated with 2.5 uM DZNep or 5uM AZA for 72 h, and TSA at 100 nM for 24 hours. For AZA treatment, the medium was replaced with freshly added AZA for every 24 h. For co-treatment of cells with DZNep and TSA, DZNep was added for 48 h followed by TSA for an additional 24 h. In total, there were seven different drug treatments (AZA, TSA, DZNep, AZA+TSA, DZNep+AZA, DZNep+TSA, DZNep+AZA+TSA). One group of untreated MCF-7 cells served as the control. Each treatment has 3 technical replicates.
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| Contributor(s) |
Sun F, Wu Z, Yu Q |
| Citation(s) |
19934278 |
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| Submission date |
Aug 11, 2009 |
| Last update date |
Mar 21, 2012 |
| Contact name |
qiang yu |
| E-mail(s) |
[email protected]
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| Organization name |
GIS
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| Street address |
BIOPOLIS STREET
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| City |
SINGAPORE |
| ZIP/Postal code |
138672 |
| Country |
Singapore |
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| Platforms (1) |
| GPL2700 |
Sentrix HumanRef-8 Expression BeadChip |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA118523 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE17589_RAW.txt.gz |
2.4 Mb |
(ftp)(http) |
TXT |
| GSE17589_normalized.txt.gz |
2.6 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
| Processed data are available on Series record |
| Processed data provided as supplementary file |
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