Genomics

Dataset Information

159

Whole genome epigenetic sequencing on DNA from infarcted non-infarcted left ventricle of WT and NEIL3-deficient mice subjected to myocardial infarction


ABSTRACT: Myocardial infarction (MI) triggers a reparative response involving fibroblast proliferation and differentiation driving extracellular matrix modulation necessary to form a stabilizing scar. Recently, it was shown that a genetic variant of the base excision repair enzyme endonuclease VIII-like 3 (NEIL3) was associated with increased risk of MI in humans. Here, we report elevated myocardial NEIL3 expression in heart failure patients and marked myocardial upregulation of Neil3 following MI in mice, especially in a fibroblast-enriched cell fraction. Neil3-/-mice showed increased mortality after MI compared to WT, caused by myocardial rupture. Epigenomic analysis suggested dysregulated myofibroblast proliferation and differentiation in Neil3-/-hearts and several differentially expressed genes were downstream targets of differentially methylated/hydroxymethylated transcriptional regulators. Furthermore, proliferation of Vimentin+ and SMA+ (myo)fibroblasts was increased in Neil3 -/-hearts following MI. We propose that NEIL3-dependent modulation of epigenetic DNA methylation regulates cardiac fibroblast proliferation and thereby controls extracellular matrix modulation after MI. Overall design: Genomic DNA from infarcted and non-infarcted LV of WT and Neil3-/- C57BL/6 mice obtained three days after induced myocardial infarction were subjected to 5mC and 5hmC sequencing using Illumina Hiseq 2000

INSTRUMENT(S): Illumina HiSeq 2000 (Mus musculus)

SUBMITTER: Katja Scheffler 

PROVIDER: GSE90057 | GEO | 2017-01-01

SECONDARY ACCESSION(S): PRJNA354387

REPOSITORIES: GEO

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Publications


Myocardial infarction (MI) triggers a reparative response involving fibroblast proliferation and differentiation driving extracellular matrix modulation necessary to form a stabilizing scar. Recently, it was shown that a genetic variant of the base excision repair enzyme NEIL3 was associated with increased risk of MI in humans. Here, we report elevated myocardial NEIL3 expression in heart failure patients and marked myocardial upregulation of Neil3 after MI in mice, especially in a fibroblast-en  ...[more]

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