The landscape of DNA repeat elements in human heart failure

Haider, Syed, Cordeddu, Lina, Robinson, Emma, Movassagh, Mehregan, Siggens, Lee, Vujic, Ana, Choy, Mun-Kit ORCID: https://orcid.org/0000-0003-3998-0774, Goddard, Martin, Lio, Pietro and Foo, Roger (2012) The landscape of DNA repeat elements in human heart failure. Genome Biology, 13 (10). R90. ISSN 1474-760X

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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.

Item Type:	Article (Article)
Peer-reviewed:	Yes
Date Deposited:	02 Nov 2023 08:17
Publisher:	BMC
Additional Information:	This is an Open Access article published in Genome Biology, by BMC.
Divisions:	Faculties > Science and Engineering
Subject terms:	Adult, Aged, Child, Preschool, DNA Methylation, Gene Expression Regulation, Genome, Human, Genomic Instability, Heart Failure, Humans, Male, Middle Aged, Myocardium, Repetitive Sequences, Nucleic Acid, Myocardium, Humans, Genomic Instability, DNA Methylation, Gene Expression Regulation, Repetitive Sequences, Nucleic Acid, Genome, Human, Adult, Aged, Middle Aged, Child, Preschool, Male, Heart Failure, Adult, Aged, Child, Preschool, DNA Methylation, Gene Expression Regulation, Genome, Human, Genomic Instability, Heart Failure, Humans, Male, Middle Aged, Myocardium, Repetitive Sequences, Nucleic Acid, 05 Environmental Sciences, 06 Biological Sciences, 08 Information and Computing Sciences, Bioinformatics
URI:	https://e-space.mmu.ac.uk/id/eprint/632797
DOI:	https://doi.org/10.1186/gb-2012-13-10-r90
ISSN	1474-760X
e-ISSN	1465-6906

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