|
| Status |
Public on Dec 06, 2017 |
| Title |
HDAC inhibitor SAHA reverses inflammatory gene expression in diabetic endothelial cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
While histone deacetylase (HDAC) inhibitors are thought to regulate gene expression by post-translational modification of histone as well as non-histone proteins. While histone hyperacetylation has long been considered the paradigmatic mechanism of action, recent genome-wide profiles indicate more complex interactions with the epigenome. In particular, HDAC inhibitors also induce histone deacetylation at the promoters of highly active genes, resulting in gene suppression. This was linked to the loss of histone acetyltransferase (HAT) binding. To illustrate pre-clinical utility of the HDAC inhibitor SAHA as a therapeutic, we show reversal of diabetes-associated EP300 target genes in diabetic HAECs of primary origin. These results were confirmed using SAHA, C646 (EP300/CREBBP inhibitor) or EP300 siRNA. These findings suggest the inhibition of gene expression by SAHA is mediated by EP300 function and provide a rationale for clinical trials of safety and efficacy in patients with diabetes.
|
| |
|
| Overall design |
Human aortic endothelial cells from a diabetic and non-diabetic individual were stimulated with DMSO (control), SAHA (2 μM, HDAC inhibitor) or C646 (10 μM, EP300 inhibitor) for 12 hours, or EP300 siRNA or non-target siRNA (control) for 4 hours, followed by 48 hours in fresh media. Study performed in triplicate.
|
| |
|
| Contributor(s) |
Rafehi H, Kaspi A, Zeimann M, Okabe J, Karagiannis TC, El-Osta A |
| Citation(s) |
28886276 |
| |
| Submission date |
Jan 21, 2016 |
| Last update date |
Jul 09, 2019 |
| Contact name |
Assam El-Osta |
| Organization name |
Baker Heart and Diabetes Institute
|
| Lab |
Human Epigenetics
|
| Street address |
75 Commercial Road
|
| City |
Melbourne |
| ZIP/Postal code |
3004 |
| Country |
Australia |
| |
|
| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (30)
|
|
| Relations |
| BioProject |
PRJNA309443 |
| SRA |
SRP068733 |
Less...
More...