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Two Enzymes Stamp DNA with "Turn Off" Signal
DNA methylation leaves indicators, or "marks", on the genome. There is evidence that these "marks" are strongly influenced by external factors such as environment and diet.
University of Cambridge researchers have found that this process is different in diseased and normal hearts. Linking all these things together suggests a "missing link" between environmental factors and heart failure.
The new data collected greatly benefits a field that is still in its scientific infancy and is a significant leap from where research was, even 18 months ago.
Researcher Roger Foo explains: "By going wider and scanning the genome in greater detail, we now have a clearer picture of the 'fingerprint' of the missing link - where and how epigenetics in heart failure may be changed and the parts of the genome where diet or environment or other external factors may affect outcomes."
The study originally began by investigating the differences in DNA methylation found in the human heart. Researchers compared data from a small number of people with end-stage cardiomyopathy (enlarged heart), who were undergoing heart transplants with the healthy hearts of age-matched, road traffic accident victims.
Study findings deepen our understanding of the genetic changes that can lead to heart disease and how these can be influenced by our diet and our environment. The findings can potentially open new ways for identifying, managing and treating heart disease.
DNA makes up our genes out of four "bases" or nucleotides cytosine, guanine, adenine and thymie, often abbreviated to C, G, A and T. Methylation is the addition of a methyl group (CH3) to the cytosine base.
When added to cytosine, the methyl group is recognised differently by proteins which alters how the gene is turned on or off, or expressed.
DNA methylation is a crucial part of normal development, allowing different cells to become different tissues despite having the same genes. As well as occuring during development, DNA methylation continues throughout our lives in a response to environmental and dietary changes, which sometimes lead to disease.
As a result of the study, Foo likens DNA methylation to a fifth nucleotide: "We often think of DNA as being composed of four nucleotides. Now, we are beginning to think there is a fifth the methylated C."
Foo adds: "...and more recent basic studies now show us that our genome has even got 6th, 7th and 8th nucleotides... in the form of further modifications of cytosines. These are hydroxy-methyl-Cytosine, formylCytosine and carboxylCytosine = hmC, fC and caC! These make up an amazing shift in the paradigm…"
As in most studies, as one question is resolved, other mysteries arise. The study shows that we are still on the frontier of epigenetics and are only just beginning to understand the link between the life we lead and the body that results.