 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on May 31, 2015 |
| Title |
Genome-wide maps of H3K9me3 and H3K4me3 state in failing heart with or without chaetocin in animal model |
| Organism |
Rattus norvegicus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Epigenetic status has been linked to cardiac hypertrophy and heart failure. Histone deacetylase inhibitors are promising drugs for preventing cardiac remodeling. We previously demonstrated very different patterns of histone H3 lysine 9 trimethylation (H3K9me3) and histone H3 lysine 4 trimethylation (H3K4me3) in failing hearts compared to control hearts in both animal models and clinical heart specimens. Here, we focused on a heart failure-specific histone modification, H3K9me3, and investigated the prognostic efficacy of administering a histone H3K9 methyltransferase inhibitor, chaetocin, to Dahl salt-sensitive rats, an animal model of heart failure. Chaetocin delayed the timing of transition from cardiac hypertrophy to heart failure, and prolonged survival in this animal model. Mitochondrial dysfunction was improved with inhibitor use in the failing heart. ChIP-seq analysis demonstrated that heart failure caused an increase in H3K9me3 alignments in thousands of repetitive elements, including regions neighboring mitochondrial genes, and a corresponding reduction of this effect with inhibitor use. However, at 35 loci, heart failure was conversely associated with a reduction in H3K9me3 alignments, and inhibitor use reversed this effect. These data suggest that excessive heterochromatinization of repetitive elements in the failing heart might impair pumping function with mitochondrial gene silencing. H3K9 methyltransferase inhibitors may be a promising novel therapy for chronic heart failure.
|
| |
|
| Overall design |
Examination of 2 different histone modifications in 3 groups of rats.
|
| |
|
| Contributor(s) |
Ono T, Kaneda R |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
May 23, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Ruri KANEDA |
| Organization name |
Jichi Medical University
|
| Street address |
3311-1 Yakushiji
|
| City |
Shimotsuke |
| State/province |
Tochigi |
| ZIP/Postal code |
3290498 |
| Country |
Japan |
| |
|
| Platforms (1) |
| GPL14844 |
Illumina HiSeq 2000 (Rattus norvegicus) |
|
| Samples (7)
|
|
| Relations |
| BioProject |
PRJNA284798 |
| SRA |
SRP058660 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE69194_RAW.tar |
6.3 Gb |
(http)(custom) |
TAR (of WIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
|
|
|
|
 |
Less...
More...