Abstract
BackgroundThe epigenomes of healthy and diseased human hearts were recently examined by genome-wide DNA methylation profiling. Repetitive elements, heavily methylated in post-natal tissue, have variable methylation profiles in cancer but methylation of repetitive elements in the heart has never been examined.ResultsWe analyzed repetitive elements from all repeat families in human myocardial samples, and found that satellite repeat elements were significantly hypomethylated in end-stage cardiomyopathic hearts relative to healthy normal controls. Satellite repeat elements are almost always centromeric or juxtacentromeric, and their overexpression correlates with disease aggressiveness in cancer. Similarly, we found that hypomethylation of satellite repeat elements correlated with up to 27-fold upregulation of the corresponding transcripts in end-stage cardiomyopathic hearts. No other repeat family exhibited differential methylation between healthy and cardiomyopathic hearts, with the exception of the Alu element SINE1/7SL, for which a modestly consistent trend of increased methylation was observed.ConclusionsSatellite repeat element transcripts, a form of non-coding RNA, have putative functions in maintaining genomic stability and chromosomal integrity. Further studies will be needed to establish the functional significance of these non-coding RNAs in the context of heart failure.
Highlights
The epigenomes of healthy and diseased human hearts were recently examined by genome-wide DNA methylation profiling
Interspersed long interspersed nuclear element (LINE) and short interspersed nuclear element (SINE) are found throughout the genome, whereas satellite (SAT) elements are largely confined to centromeres or centromere-adjacent heterochromatin
For the purpose of our comparison, we observed that SINE-1 (SINE1/7SL), LINE-1 (L1), Satellite (SAT) and endogenous retrovirus 1 (ERV1) families were highly representative, having 32, 13, 8 and 8 repeat sequences, respectively
Summary
The epigenomes of healthy and diseased human hearts were recently examined by genome-wide DNA methylation profiling. Repetitive elements and retrotransposons make up at least 45% of the human genome and are expressed as non-coding transcripts in different tissues [3,4] but their expression in the heart has never been examined. DNA sequences of repetitive elements are highly methylated in postnatal tissues but can be variably methylated in cancer [7]. In a genome-wide DNA methylation screen of nerve sheath tumors, Beck and colleagues [8] found that SAT repeats, but not other repetitive elements, are hypomethylated and aberrant methylation of these was associated with the transition from healthy cells to malignant disease
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