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Multiscalar nucleosome dynamics in silico ‐ Role of DNA and histone tails
Author(s) -
Sharma Shantanu,
Ding Feng,
Dokholyan Nikolay V
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a282-c
Subject(s) - nucleosome , histone , linker dna , chromatin , chromatosome , biophysics , dna , histone code , biology , chemistry , microbiology and biotechnology , genetics
Nucleosomes form the fundamental building blocks of chromatin. Subtle modifications of histones tails regulate gene expression, necessitating a study of nucleosome dynamics at atomic levels. We report a novel multi‐scale nucleosome model, having a simplified model for rapid discrete molecular dynamics simulations and an all‐atom model for detailed structural investigation. Using a simplified structural model, we perform equilibrium simulations of a single nucleosome at various temperatures. We further reconstruct all‐atom nucleosome structures from simulation trajectories. We find that histone tails bind to nucleosomal DNA via strong salt‐bridge interactions over a wide range of temperature, suggesting a mechanism of chromatin structural organization, whereby histone tails regulate inter‐ and intra‐nucleosomal assemblies via binding with nucleosomal DNA. We identify histone core residues, termed cold sites, which retain a significant fraction of contacts with adjoining residues throughout the simulation, indicating their functional role in nucleosome organization. Cold sites are clustered around H3‐H3′, H2A‐H4′ and H4‐H2A′ inter‐histone interfaces indicating necessity of these contacts for nucleosome stability. Essential dynamics analysis shows bending across the H3‐H3′ is a prominent mode of intra‐nucleosomal dynamics. We postulate that effects of salts on mononucleosomes can be modeled in DMD by modulating histone‐DNA interaction potentials. Fluctuations in nucleosomal DNA vary significantly along the DNA sequence, suggesting that a small fraction of histone‐DNA contacts contribute to nucleosomal dynamics. Our findings suggest that histone tails have a direct role in stabilizing higher order chromatin structure, mediated by salt bridge interactions with adjacent DNA.