Albany 2015:Book of Abstracts
June 9-13 2015
©Adenine Press (2012)
Combined Influence of Linker DNA and Histone Tails on Nucleosome Dynamics as Revealed by Microsecond Molecular Dynamics Simulations
Nucleosomes are elementary units of chromatin compaction, which play crucial role in genome functioning. X-ray crystallographic studies of the nucleosome core consistently revealed a compact structure that has approximately 147 DNA base pairs wrapped in a 1.7 superhelical turn around histone octamer. However, it is becoming appreciated that nucleosomes are dynamic entities with conformational plasticity at various levels, which is necessary to fulfill their functions.
We have constructed a full nucleosome atomistic model with the linker DNA segments and histone tails based on the available X-ray structure of the nucleosome core. We perform multiple molecular dynamics (MD) simulations on microsecond time scale at different ionic conditions, and with several force fields. Here we report a detailed analysis of nucleosome dynamics, conformational changes with respect to the available X-ray structure of the core, and protein-DNA interactions. We find that histone tails condense onto DNA, including the linker DNA, may undergo order-disorder conformational transitions and may affect the conformation, stability and dynamics of both nucleosomal and linker DNA. The linker DNA is flexible enough to accommodate various bent conformations within the thermal fluctuation limit. DNA binding sites in the nucleosomal core show varying stability and potential for rearrangement of DNA path within the core. Our findings are important for understanding of the interplay between histone tails and DNA in view of nucleosome functional dynamics and role of post-translational modifications located within the histone tails.
This research was supported by the Intramural Research Programs of the National Library of Medicine and the National Cancer Institute, NIH. AS was supported by the US-Russia Collaboration in the Biomedical Sciences NIH visiting fellows program. Development of nucleosome visualization algorithms was supported by the Russian Science Foundation (RSF grant No. 14-24-00031).
Alexey K. Shaytan1
1 National Center for Biotechnology Information