DNA Methylation at single molecule level

Just heard this talk….Nanomechanics of DNA Methylation!!! Always drew my interest as it is one of the major epigenetic modifications leading to gene silencing. Gene silencing occurs when a cell develops or exercises the ability to prevent or reduce the expression of a certain gene. These modifications do not alter the sequence of the DNA but they affect how the genes are read by the cell. Every tumor without any exceptions, has varied frequencies of DNA methylation pattern, indicating an altered genome. No doubt, it has been studied to be a cause of breast cancer, ovarian cancer, colorectal cancer, head and neck cancer, aging, Rett Syndrome and many more. Already epigenetic therapies towards drug development involving cancer is driven by DNA methylation inhibitors (FDA approved) like 5-azacytidine (Vidaza), 5 aza-2/-deoxycytidine, Decitabine (Dacogen) and there are many more in various phases of clinical trials. Henceforth, seeing this at a single molecule level becomes even more exciting. There have been recent papers studying these, but the one which almost resembled the work done by Csaba I. Pongor was by Kaur et al “Hydrophobicity of methylated DNA as a possible mechanism for gene silencing.” Physical biology 9, no. 6 (2012): 065001. While both were able to observe a shorter contour length in the methylated form of the DNA, and an increase in persistence length in the methylated form, but the interpretations seemed quite different, Csaba’s work had in additional a lowering of stress modulus on methylation. I would have certainly liked to observe a titration study on the degree of methylation and observed the effects, likewise done by kaur et al, but still beautiful work!! Well it is indeed fascinatinig how just adding a single methyl group to the DNA can give such huge variations to it. Surely more work needs to be done at single molecule level to understand this mechanism further and I would be looking forward to it.


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