The landscape of DNA repeat elements in human heart failure
- Equal contributors
1 Computer Laboratory, William Gates Building, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0FD
2 Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke's Centre for Clinical Investigation, Level 6, Hills Road, Cambridge, CB2 0QQ
3 Department of Histopathology, Papworth Hospital, Papworth Everard, Cambridge, UK
4 Cardiovascular Research Institute, National University Health System, Singapore
5 Genome Institute of Singapore, Singapore 138672, Singapore
Genome Biology 2012, 13:R90 doi:10.1186/gb-2012-13-10-r90Published: 3 October 2012
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.
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.
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.