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The landscape of DNA repeat elements in human heart failure.

Published version
Peer-reviewed

Type

Article

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Authors

Haider, Syed 
Cordeddu, Lina 
Robinson, Emma 
Movassagh, Mehregan 
Siggens, Lee 

Abstract

BACKGROUND: The 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. RESULTS: We 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. CONCLUSIONS: Satellite 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.

Description

Keywords

Adult, Aged, Child, Preschool, DNA Methylation, Gene Expression Regulation, Genome, Human, Genomic Instability, Heart Failure, Humans, Male, Middle Aged, Myocardium, Repetitive Sequences, Nucleic Acid

Journal Title

Genome Biol

Conference Name

Journal ISSN

1474-760X
1474-760X

Volume Title

13

Publisher

Springer Science and Business Media LLC