Joint Effect of Histone H1 Amino Acid Sequence and DNA Nucleotide Sequence on the Structure of Chromatosomes: Analysis by Molecular Modeling Methods

Abstract

A chromatosome consisting of a nucleosome core, linker DNA, and linker histone (LH) is an important structural element of chromatin and plays a role in replication and transcription regulation. There are two experimentally confirmed modes of LH binding to the nucleosome and linker DNA that differ in their geometry: on-dyad and off-dyad binding. It was shown that the LH amino acid sequence influences the type of histone binding and the conformation of the chromatosome. However, the geometry of linker DNA bound with LH also changes. Thus, the mutual influence of these factors and the molecular basis determining the type of LH binding to nucleosomes remain unclear. In this study, molecular modeling methods, including homology modeling, atom–atom interaction analysis, and DNA deformation energy analysis, were applied to study the joint effect of the LH amino acid sequence and the DNA nucleotide sequence on the configuration of the chromatosome. The known crystal and NMR structures of the chromatosome for atom–atom interactions of LH and DNA, as well as the energy of DNA deformation in these structures for various DNA sequences, were analyzed. For various LH H1 variants, the analysis was carried out using homology modeling methods. Sequence-dependent differences in the bending energy of the linker DNA for two different conformations of the chromatosome were found, and nucleotide sequences preferred for these structures were proposed. As a result of the analysis, it was shown that the DNA nucleotide sequence, along with the LH amino acid sequence, influences the type of binding to the nucleosome. Hypotheses for experimental verification have been formulated, according to which the type of LH binding can change with different DNA nucleotide sequences.