Physicochemical analysis of electrostatic foundation for DNA-protein interactions in chromatin transformations.

Electrostatic interactions between DNA and DNA-packaging proteins, the histones, contribute substantially to stability of eukaryotic chromatin on all levels of its organization and are particularly important in formation of its elementary structural unit, the nucleosome. The release of DNA from the histones is an unavoidable stage in reading the DNA code. In the present review, we discuss the disassembly/assembly process of the nucleosome from a thermodynamic standpoint by considering it as a competition between an excess of polyanions (DNA and acidic/phosphorylated domains of the nuclear proteins) for binding to a limited pool of polycations (the histones). Results obtained in model systems are used to discuss conditions for the electrostatic component of DNA-protein interactions contributing to chromatin statics and dynamics. We propose a simple set of "electrostatic conditions" for the disassembly/assembly of nucleosome/chromatin and apply these to put forward a number of new interpretations for the observations reported in literature on chromatin. The approach sheds light on the functions of acidic domains in the nuclear proteins (nucleoplasmin and other histone chaperones, HMG proteins, the activation domains in transcriptional activators). It results in a putative explanation for the molecular mechanisms behind epigenetic regulation through histone acetylation, phosphorylation, and other alterations ("the language of covalent histone modification"). We also propose a new explanation for the role of phosphorylation of C-terminal domain of RNA polymerase II for regulation of the DNA transcription. Several other examples from literature on chromatin are discussed to support applicability of electrostatic rules for description of chromatin structure and dynamics.