Your DNA is also affected by Vitamins A & C and not good just for your health. The Babraham Institute Researchers and their international collaborators have discovered how vitamins A and C act to modify the epigenetic memory held by cells. This is an insight, which is significant for regenerative medicine and our ability to reprogram cells from one identity to another. They published their research results in Proceedings of the National Academy of Science (PNAS).
For regenerative medicine, the best possible is to be able to generate a cell that can be directed to become any other cell, such as brain cells, heart cells and lung cells. Cells with this ability are present in the early embryo and give rise to the many different cells types in the body. We need to be able to force adult cells from a patient to regress back to possessing embryonic-like capabilities and to forget their previous identity for the purpose of regenerative medicine.
Identity of a cell is established at the DNA level by epigenetic changes to the DNA that don’t alter the order of the DNA letters but control which parts of the genome can be read and accessed. Every cell type has a unique epigenetic fingerprint that enforces and maintains specific patterns of gene expression appropriate to the cell type. In order to reverse cells back to the naïve pluripotent state this epigenetic layer of information has to be lost to open up the full genome again.
The Babraham Institute, UK, University of Stuttgart, Germany and University of Otago, New Zealand researchers worked together to uncover how vitamins A & C affect the erasure of epigenetic marks from the genome. The epigenetic modification was particularly looked at where a methyl chemical tag is added to the C letters in the DNA sequence. Low levels of this C tagging, called cytosine methylation, are shown in embryonic stem cells, but in the established cell types much more of the genome is marked by this modification. Removing the methyl tags from the DNA, called demethylation, is a central part of achieving pluipotency and wiping epigenetic memory.
Vitamin A enhances epigenetic memory erasure in naïve ESC by increasing the amount of TET (family of enzymes responsible for active removal of the methyl tags) enzymes in the cell, a greater removal of methyl tags from the C letters of the DNA sequence. They found that vitamin C boosted the activity of the TET enzymes by regenerating a co-factor required for effective action.
Dr. Ferdinand von Meyenn, postdoctoral researcher at the Babraham Institute and co-first author, said “Both vitamins A and C act individually to promote demethylation, enhancing the erasure of epigenetic memory required for cell reprogramming.” They found that the mechanisms of how vitamins A and C enhance demethylation are different, yet synergistic.
This improved understanding of the effect of vitamin A on the TET2 enzyme explains why a proportion of patients with acute promyelocytic leukemia are resistant to effective combination treatment with vitamin A. This could point the way to better management of the vitamin A resistant cases.
This study was funded by The Wellcome Trust, the Biotechnology and Biological Sciences Research Council, the Medical Research Council, the European Union EpiGeneSys Network of Excellence, the European Union BLUEPRINT Consortium, the Human Frontier Science Program, the Swiss National Science Foundation/Novartis and the German Research Foundation.
–Dr Fredda Branyon