Effect of nuclear electrostatic potential on the nucleoplasmic distribution of histones and nucleosome stability

Differences in the density of heterochromatic and euchromatic regions are often assumed to play an important role in determining the transcriptional state of chromatin by influencing its accessibility to transcription factors. Yet, experiments show that even the most densely packed chromatin domains are readily accessible to transcription factors. Thus, the molecular mechanisms underlying differences in the transcriptional states of hetero- and euchromatin remain poorly understood. In this study, using electrically charged mEGFP probes, we demonstrated that heterochromatin and euchromatin differ not only in density but also in the magnitude of the local electrostatic potential. Furthermore, the nucleoplasmic distribution of electrically charged proteins, such as histone-chaperone complexes, was found to correlate with the local electrostatic potential. Estimates based on experimental data have also shown that the difference in electrostatic potentials between heterochromatic and euchromatic regions could lead to unequal nucleosome stability in them, which was successfully confirmed experimentally. Subsequent theoretical calculations showed that this could shift the balance in the DNA-binding competition between transcription factors and nucleosomes, thereby explaining experimental observations that heterochromatin is less transcriptionally active than euchromatin. Overall, our study suggests the existence of a nuclear electrostatic potential-mediated pathway that may be involved in the regulation of gene transcription.