Repetition may help the brain learn, but it can be rough on the heart. Researchers in Cambridge, U.K. have found that DNA repeats in damaged hearts are hypomethylated, and that’s associated with increased transcription.
In research they published last year, the team did the first whole-genome analysis of differential DNA methylation in so-called “end-stage cardiomyopathic (EsCM)” human hearts and control healthy hearts. They found differential DNA methylation at the DUX4 locus, which is within a repeat array. That made the team wonder about other repetitive elements in the genome.
They looked at their DNA methylation data again, but focused on repeats. (Although others had reported that transcription is increased in aged mouse hearts as silencing is lost at centromeres, no one had looked at DNA methylation of repeats like this in heart tissue, they said.) Satellite (SAT) repeats, which are at or near centromeres, were significantly differentially hypomethylated in EsCM versus healthy hearts. No such pattern was obvious for other types of repeats, except for SINE1/7SL, which appeared to have more DNA methylation.
The researchers analyzed three of the SAT repeats in detail. They validated the hypomethylation finding, then looked at transcription. Transcripts of all three repeats were upregulated by up to 27-fold in EsCM hearts compared with healthy controls. In addition, H3K36me3, a histone mark of increased transcription, was enriched in the repeat regions.
The researchers state that more work is needed to figure out whether the DNA methylation changes cause health problems or are the result of those problems.
Get to the heart of the matter at Genome Biology, October 2012.