Bumpy DNA

1/12/2009

 All cells making up the human body contain the same DNA in their nucleus, the DNA entailing about 30,000 genes and each gene containing instructions for a protein. Despite this sameness, the cells in different parts of our body are very different due to many factors, a key one being that the level of expression of genes into protein is highly regulated and differs strictly from cell to cell. One rather common regulation mechanism involves methylation of one of the four bases of DNA, cytosin. Researchers find that the long DNA in human cells show spots of methylated cytosins, the methylation being correlated with the expression level of the genes near the spots. In fact, medical researcher relate several cancers to improper methylation of DNA. Despite the common occurrence of regulation by methylation, researchers have little understanding how methylation, that changes an H (hydrogen atom) for a CH_3 (methyl group) here and there, i.e., just adds small bumps on a rather bulky DNA molecule, affect the physical properties of DNA such that expression levels are altered. It was found that there are proteins that can recognize the CH_3 groups, i.e., the bumps, on the DNA, but researchers have a hunch that methylation does affect DNA properties directly, i.e., without protein markers, but do not know which properties. In a collaboration between bioengineers measuring the passing of DNA through nanopores and computational biologists simulating this process with NAMD (see also the Nov 2005 highlight stretchable DNA) first hints emerge that methylation does in fact alter DNA's ability to stretch itself through a nanopore. As reported recently, pulling DNA electrostatically through nanopores is easier for methylated than for unmethylated DNA, as seen both in experiment and simulation. The findings promise insight into an important chapter in the field of genetic control. More on our methylated DNA website. See also our recentbiotechnology review.

Nanoelectromechanics of methylated DNA in a synthetic nanopore. Utkur M. Mirsaidov, Winston Timp, Xueqing Zou, Valentin Dimitrov, Klaus Schulten, Andrew P. Feinberg, and Greg Timp. Biophysical Journal, 96:L32-L34, 2009.