The nucleosome core particle is at the lowest level of DNA compaction, a mechanism that enables the DNA to fit inside the cell nucleus. Multiple nucleosomes, connected to each other like beads on a...Show moreThe nucleosome core particle is at the lowest level of DNA compaction, a mechanism that enables the DNA to fit inside the cell nucleus. Multiple nucleosomes, connected to each other like beads on a string, can stack tightly together to form the chromatin fiber. The compact form of this structure hinders external proteins and enzymes from accessing the nucleosomal DNA and using them in fundamental DNA processes. Nucleosome breathing is a process in which access is facilitated by the transient unwrapping of the nucleosome, thereby exposing the otherwise occluded DNA. This thesis investigates the nucleosome breathing mechanism in a dinucleosome system, a sub-structure of the chromatin fiber where two identical nucleosomes with varying DNA sequence are connected by a piece of linker DNA of varying length. The accessibility of the nucleosomal binding sites is modelled through a statistical model, expressing the breathing process in terms of the adsorption energy of the binding sites and the elasticity of the bent DNA in a dinucleosome configuration. The elastic energy of the bent linker DNA and nucleosomal DNA during the breathing process is estimated through a Monte-Carlo simulation. The results make clear that binding sites in such a dinucleosome structure are much more accessible than binding sites in a mononucleosome. Our findings show that the length of the linker DNA and the sequence of the nucleosomes are a determining factor of the dinucleosome configuration, thereby suggesting that these parameters play an important role in regulating the accessibility of higher order structures such as the chromatin fiber.Show less
