Molecular Medicine Israel

High-Throughput Epigenetics Analyses

Emerging technologies help researchers draw mechanistic links between metabolism and epigenetic modification of DNA

Chemical groups tacked onto DNA or histone proteins regulate how and when genes are expressed. Environmental signals can change the placement of these epigenetic tags, but researchers have had trouble pinning down how phenomena such as diet, inflammation, or social stress are converted into instructions that tweak gene functions.

Researchers have known for decades how some aspects of metabolism can wield epigenetic effects: breakdown products formed during sugar or protein digestion, for example, can be converted into chemical tags that epigenetically modify DNA or histones. But even a process as fundamental as turning glucose into cellular fuel can occur via distinct pathways that dynamically change based on a cell’s immediate environment and state. So a cancer cell and a healthy one might digest sugars in distinct ways—and thus have different metabolites available for making epigenetic marks.

Knowing which metabolites can regulate gene function—and whether they do so by epigenetic means, binding to transcription factors, or other routes—is crucial to developing better drugs. Fortunately, studies demonstrating precisely how metabolism alters epigenetics have recently emerged, triggered in part by better technologies. Whole genome sequencing methods now enable researchers to map epigenetic changes across the entire genome, and high-throughput approaches such as liquid chromatography and mass spectrometry can track changes in hundreds of metabolites at once.

Also, recent research has revealed connections between aberrant metabolism and epigenetic changes in cancer cells, leading scientists to examine whether metabolic changes may be driving epigenetic ones. “These are two fields that operated independently for years,” says Jason Locasale, a cancer researcher at Duke University. “In the last 10 years, a confluence of different observations of altered metabolism in cancer cells and developmental biology has led to many of these new studies.”…..

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