|
| Status |
Public on Nov 05, 2008 |
| Title |
ING4 ChIP-chip in HT1080 cells |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by genome tiling array
|
| Summary |
Aberrations in chromatin dynamics play a fundamental role in tumorigenesis, yet relatively little is known of the molecular mechanisms linking histone lysine methylation to neoplastic disease. ING4 (Inhibitor of Growth 4) is a native subunit of an HBO1 histone acetyltransferase (HAT) complex and a tumor suppressor protein. Here we show a critical role for the specific read-out of histone H3 trimethylated at lysine 4 (H3K4me3) by the ING4 PHD finger in mediating ING4 gene expression and tumor suppressor functions. The interaction between ING4 and H3K4me3 augments the acetylation activity of HBO1 on H3 tails, and drives H3 acetylation at ING4 target promoters to effect a DNA damage-dependent gene expression program. Further, ING4 facilitates apoptosis in response to genotoxic stress and inhibits anchorage-independent cell growth, and these functions are dependent on ING4 interactions with H3K4me3. Together, our results demonstrate a mechanism for brokering crosstalk between H3K4 methylation and histone H3 acetylation, and reveal a new molecular link between chromatin modulation and tumor suppressor mechanisms.
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| |
|
| Overall design |
ING4 ChIP-chip +/- Doxorubicin treatment in HT1080 cells on Nimblegen whole genome promoter array
4 samples: HT1080 cell lines stably expressing Flag-ING4 or Flag-ING4-D213A, +/- doxorubicin
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| |
|
| Contributor(s) |
Hung T, Binda O, Gozani O |
| Citation(s) |
19187765 |
| Submission date |
Oct 30, 2008 |
| Last update date |
Mar 20, 2012 |
| Contact name |
Tiffany Hung |
| E-mail(s) |
tiffany.hung@stanford.edu
|
| Organization name |
Stanford University
|
| Street address |
371 SERRA MALL
|
| City |
Stanford |
| State/province |
CA |
| ZIP/Postal code |
94305 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL6325 |
NimbleGen Homo sapiens HG18 promoter 1 of 2 |
|
| Samples (4)
|
| GSM338399 |
ING4 ChIP-chip + Doxorubicin treatment |
| GSM338400 |
ING4 PHD mutant ChIP-chip + Doxorubicin treatment |
| GSM338409 |
ING4 PHD mutant ChIP-chip |
|
| Relations |
| BioProject |
PRJNA109775 |
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