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| Status |
Public on Jul 13, 2011 |
| Title |
ChIP-on-chip of H2A variants and H3 from normal Prostate epithelial cells (PrEC) and the LNCaP cancer cell line |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by genome tiling array
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| Summary |
H2A.Z is an evolutionarily conserved H2A variant implicated in the regulation of gene expression, however its role in transcriptional deregulation in cancer remains poorly understood. Using genome-wide studies, we investigated the role of promoter-associated H2A.Z and acetylated H2A.Z (acH2A.Z) in gene deregulation and its relationship with DNA methylation and H3K27me3 in prostate cancer. Our results reconcile the conflicting reports of positive and negative roles for histone H2A.Z and gene expression states. We find that H2A.Z is enriched in a bimodal distribution at nucleosomes surrounding the transcription start sites (TSSs) of both active and poised gene promoters, whereas acH2A.Z is only localized at the TSSs of actively expressed genes. Interestingly, H2A.Z spreads across the entire promoter of inactive genes in a de-acetylated state. Gene deregulation in cancer is also associated with a reorganization of acH2A.Z and H2A.Z nucleosome occupancy across the promoter region and TSS of genes. Notably, in cancer cells we find that a gain of acH2A.Z at the TSS occurs with an overall decrease of H2A.Z levels in concert with oncogene activation. Furthermore, underacetylated H2A.Z at TSSs is increased with silencing of tumour suppressor genes. We also demonstrate that acH2A.Z anti-correlates with promoter H3K27me3 and DNA methylation. For the first time, we show that acetylation of H2A.Z is a key modification involved in gene activity in normal cells and in epigenetic gene deregulation in tumourigenesis.
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| Overall design |
ChIP samples against histones amplified and hybridised to Affymetrix Human Promoter 1.0R arrays, normalised to Input samples hybridised alongside
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| Contributor(s) |
Valdés-Mora F, Song JZ, Statham AL, Strbenac D, Robinson MD, Nair SS, Patterson KI, Tremethik DJ, Stirzaker C, Clark SJ |
| Citation(s) |
21788347 |
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| Submission date |
Dec 08, 2010 |
| Last update date |
Jan 21, 2015 |
| Contact name |
Aaron Statham |
| E-mail(s) |
a.statham@garvan.org.au
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| Organization name |
Garvan Institute of Medical Research
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| Department |
Cancer Department
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| Lab |
Epigenetics Research Laboratory
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| Street address |
384 Victoria St
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| City |
Darlinghurst |
| State/province |
NSW |
| ZIP/Postal code |
2010 |
| Country |
Australia |
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| Platforms (1) |
| GPL5082 |
[Hs_PromPR] Affymetrix Human Promoter 1.0R Array |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA135863 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE25914_RAW.tar |
643.6 Mb |
(http)(custom) |
TAR (of BAR, CEL) |
| Processed data provided as supplementary file |
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