Proposed coupling of chromatin replication, hormone action, and cell differentiation

DNA replication in isolated nuclei is highly dependent on the availability of soluble proteins from the cell cytoplasm. Activity is distributed nonrandomly among the different proteins, and the range of proteins that are required for optimal DNA replication varies with the fractions of DNA being replicated. Support of DNA replication has been correlated with the uptake of these proteins by nuclei and their integration into an immature form of the newly replicated chromatin; the latter has been shown by density analysis to be richer in protein content than the bulk of nonreplicating chromatin. Pulse labeling of DNA in living cells has revealed that a similar protein-rich chromatin is formed as an intermediate in chromatin replication in vivo; however, this form rapidly matures by the exclusion of proteins. The dependency of DNA replication on the presence of soluble cytoplasmic proteins and the physical association of these entities with newly replicated chromatin prompt the proposal that availability of specific proteins may play an important role in determining the ultimate genetic expressability of the matured chromatin and thus the cell phenotype. The finding that dexamethasone, a steroid that regulates the expression of several genes and directs the differentiation of certain cells, can modify the uptake of proteins in isolated nuclei is in accord with this hypothesis.