Condensation of DNA and chromatin.

N. Korolev (School of Biological Sciences, Nanyang Technological University, Singapore)

Abstract

The carrier of genetic information and major component of chromatin, DNA, is a densely charged polyanion. Electrostatic interactions between DNA and DNA-packaging proteins contribute decisively to formation of elementary unit of chromatin, the nucleosome, and are also important in chromatin folding into higher-order structures. We investigate condensation of DNA and chromatin and find that electrostatics and polyelectrolyte character of DNA play dominant role in these processes. By comprehensive experimental studies and using novel oligocationic ligands, we suggest simple universal equation describing DNA condensation as a function of oligocation, DNA and monovalent salt concentrations and including the ligand-DNA binding constant. We found that similar dependence was also observed in condensation of the nucleosome arrays. Next, we studied how general electrostatic and specific structural alterations caused by lysine acetylations in the histone tails influence formation of 30-nm chromatin fibre and inter-molecular nucleosome array association. For the first time, a structural model is suggested which explains critical dependence of chromatin fibre folding on acetylation of the single lysine at position 16 of the histone H4. Exceptional importance of the H4 Lys 16 acetylation in general and gene specific transcriptional activation has been known for many years but no structural basis for this effect has yet been proposed.