Nucleosome Crowding in Chromatin Slows the Diffusion but Can Promote Target Search of Proteins.

ABSTRACT: Dynamics of nuclear proteins in crowded chromatin has only been poorly understood. Here, we address the diffusion, target search, and structural dynamics of three proteins in a model chromatin using coarse-grained molecular simulations run on the K computer. We prepared two structures of chromatin made of 20 nucleosomes with different nucleosome densities and investigated dynamics of two transcription factors, HMGB1 and p53, and one signaling protein, ERK, embedded in the chromatin. We found fast and normal diffusion of the nuclear proteins in the low-density chromatins and slow and subdiffusional movements in the high-density chromatin. The diffusion of the largest transcription factor, p53, is slowed by high-density chromatin most markedly. The on rates and off rates for DNA binding are increased and decreased, respectively, in the high-density chromatin. To our surprise, the DNA sequence search was faster in chromatin with high nucleosome density, though the diffusion is slower. We also found that the three nuclear proteins preferred to bind on the linker DNA and the entry and exit regions of nucleosomal DNA. In addition to these regions, HMGB1 and p53 also bound to the dyad.

SUBMITTER: Kanada R 

PROVIDER: S-EPMC6588829 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature