DescriptionThis dissertation introduce a new analytical method for modeling protein-bound DNA minicircles. It is a general method that can be used for monomer, dimer, and minicircles with an arbitrary number of nucleosomes.
First, we introduce an analytical method to generate the pathway of a closed protein-bound DNA minicircle. This is a general method which can be used to connect any two open curves with well defined mathematical definitions as well as pairs of discrete systems found experimentally. We used this method to describe the configurations of torsionally relaxed, 360-base pair DNA rings with two evenly-spaced, ideal nucleosomes. We considered superhelical nucleosomal pathways with different levels of DNA wrapping and allowed for different inter-nucleosome orientations. We completed the DNA circles with the smooth connectors and studied the associated bending and electrostatic energies for different configurations in the absence and presence of salt. The predicted stable states bear close resemblance to reconstituted minicircles observed under low and high salt conditions.
Secondly, we discuss and derive analytical equations describing a Hyper-Elliptical Helix used to represent protein-free DNA. We use a circular helix for undistorted nucleosomal DNA and an elliptical helices for distorted nucleosomal DNA. We use a circular/elliptical helix, a Hyper-Elliptical Helix and two smooth connectors to describe monomers, i.e., minicircles bearing a single nucleosome, of 359 base pairs. We compute the electrostatic, bending, and twist energies for different configurations.
Finally, we use the analytical model that we developed to model and describe nucleosomal DNA minicircles with evenly spaced nucleosomes. We construct minicircles of 2064-bp length including twelve evenly spaced nucleosomes of 121 and 141 base pairs corresponding to ∼ 1.5 and ∼ 1.75 superhelical turns. We compute electrostatic and bending energies for different configurations. We repeat the same steps for a larger system of 2652-bp length so that we can construct more possible configurations.