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My main focus is transcriptomics analysis and very recently I have also started working on metabolomics. From my transcriptomic data it looks like there is a gene/protein that could potentially generate epigenetic modifications. I also have untargeted metabolomics data of equivalent experimental conditions that I plan to analyse soon hoping it will complete the picture. However, I have searched for publications linking specific metabolites with hyper/hypomethylation or chromatin structure and I have only been able to find a few references (see link below) and I got the feeling that untargeted metabolomics does not seem to be an obvious technique to observe epigenetic signatures. https://www.ncbi.nlm.nih.gov/pubmed/30125527

What metabolites would be regulated under epigenetic circumstances? Does anybody have any experience or know of any particular study that looks into this relationship between untargeted metabolomics and epigenetic modifications? Thank you very much for your help!

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This is a fascinating question, and I spent a fair amount of time looking into it. From what I've been able to find regarding the relationship between metabolics and epigenetics, it seems that metabolites drive epigenetic changes, not the other way around. This can be shown quite well by looking at cell differentiation and induced pluripotent stem cells. The epigenetic changes that happen in these processes happen due to the cell's environment.

However, epigenetic changes cause changes in transcription rates, so it can indirectly influence metabolics. The circadian clock uses this system (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392647/). Cell signaling appears to be the most significant cause of metabolic change, though. The aforementioned paper also says this:

As most metabolites are not diffusible between mitochondria and cytosol/nucleus, accurate determination of the cytoplasmic pool size is critical to understand their effects on epigenetic signaling. Although attempts have been made, so far the technology to reliably measure metabolite concentrations in different cellular compartments is lacking.

Which, I'm sorry to say, leads me to believe that there are very few metabolic pathways that have known effects on epigenetic factors. That said, there are several references in that paper which may put you on a good path forward.

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  • $\begingroup$ Thank you very much for your answer and the reference :) Indeed, it is very interesting. Maybe newer techniques such as super-resolution microscopy could help to define the metabolite concentrations in cellular compartments in the future. $\endgroup$
    – Sari
    Apr 30, 2020 at 13:38

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