INDUCTION OF H10-GENE EXPRESSION IN B16 MURINE MELANOMA-CELLS

Histone H1(0) accumulation is associated with the terminal stage of differentiation. Unlike other H1 histones, it is able to accumulate in the absence of DNA synthesis, however the transcription of its gene is cell-cycle dependent. The regulation of H1(0)-gene expression has been studied during the induced differentiation of B16 cells and during reversion of the process, which may be achieved when induced cells are released into an inducing-agent-free medium. During the earlier period of induced differentiation, H1(0) mRNA showed over-expression when the cells were still proliferating. Then the amount of H1(0) mRNA decreased as the cells became arrested in G0-G1. H1(0) mRNA half-life measurements and run-on experiments demonstrated that such modulation of the amount of mRNA originated from a transcriptional control of H1(0)-gene expression. When induced cells reverted to a proliferative undifferentiated state, H1(0) mRNA decreased very rapidly, indicating that an active process was involved in this decay. This behavior differed from that observed in rat liver hepatocytes allowed to proliferate and de-differentiate after partial hepatectomy, or in murine erythroleukemia cells when the inducing agent was removed from the culture.