Interaction of iron ions with oxygen or nitrogen monoxide in chromosomes triggers synchronous expression/suppression oscillations of compact gene groups ('genomewide oscillation'): Hypothesis

摘要

It has been proposed that the "oxygen-endogenous reductants" system responsible for oscillatory changes in the redox potential of the cell fulfills the function of a "central oscillator" by inducing synchronous oscillations of an immense array of genes in the cell genome (so-called "genomewide oscillation"). The effect of the redox potential on the genome can be mediated by copper or iron ions. Copper ions can induce oscillating change of the DNA double helix stability through the change of guanine-cytosine pair stability depending from valence state of copper ions. Iron ions can have a redox potential effect on the genome mediated by iron + thiol groups localized in chromosomes. Cyclic changes in the thiol content concomitant with oxidation of thiols to disulfides trigger oscillatory changes in the activity of multiple redox-sensitive transcription factors eventually resulting in genomewide oscillation. In the presence of nitric oxide, oscillatory changes in thiol levels in chromosomes can be induced by S-nitrosylation of thiols. The latter is catalyzed by iron ions and results in incorporation of nitric oxide into dinitrosyl complexes with thiol-containing ligands. It is not excluded that by virtue of their ability to react with S-nitrosothiols, thiols and nitric oxide, these complexes contribute to the formation of a steady-state self-regulating oscillating chemical system and thus fulfill the function of "central regulators" of genomewide oscillation. (c) 2008 Elsevier Inc. All rights reserved.