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Series GSE69194 Query DataSets for GSE69194
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
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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)
GSM1695172 input DNA
GSM1695173 H3K9me3_ChIPSeq_cont
GSM1695174 H3K9me3_ChIPSeq_HF
BioProject PRJNA284798
SRA SRP058660

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE69194_RAW.tar 6.3 Gb (http)(custom) TAR (of WIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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