Conformational transitions in closed circular DNA molecules. II. Biological implications.

A model of regulation of gene action based on the theory of conformational transitions in closed circular DNA molecules is proposed and discussed in connection with the mechanisms of cellular differentiation. The model predicts two main types of regulation of gene action (1) the change in the topological linking number of the DNA loops leading to the change in the amount of the DNA segments present in the transcriptionally active A-form and (2) the change of some nucleotide sequences in closed superhelical DNA loops resulting in conformational transitions of some of the other sequences in the same loop. The first type of regulation may explain the mechanism of terminal differentiation of the stem cells and the changes accompanying the malignant transformation. The second one may explain the variegated position effect of the gene and determination of the stem cells during ontogenesis.