Abstract Biochemical reactions typically depend on the concentrations of the molecules involved, and cell survival therefore critically depends on the concentration of proteins. To maintain constant protein concentrations during cell growth, global mRNA and protein synthesis rates are tightly linked to cell volume. While such regulation is appropriate for most proteins, certain cellular structures do not scale with cell volume. The most striking example of this is the genomic DNA, which doubles during the cell cycle and increases with ploidy, but is independent of cell volume. Here, we show that the amount of histone proteins is coupled to the DNA content, even though mRNA and protein synthesis globally increase with cell volume. As a consequence, and in contrast to the global trend, histone concentrations (i.e. amounts per volume) decrease with cell volume but increase with ploidy. We find that this distinct coordination of histone homeostasis and genome content is already achieved at the transcript level, and is an intrinsic property of histone promoters that does not require direct feedback mechanisms. Mathematical modelling and histone promoter truncations reveal a simple and generalizable mechanism to control the cell volume- and ploidy-dependence of a given gene through the balance of the initiation and elongation rates.

ABSTRACT Euglena gracilis is a suitable model system to investigate the role of zinc in the process of cell division. In zinc-deficient organisms there is a characteristic arrest of cellular proliferation, the DNA content of the cells doubles, whereas RNA and protein contents decrease. The present investigations include the growth characteristics, changes in cellular morphology at various stages in the growth cycle, quantitation of zinc uptake and incorporation of tritium-labelled precursors into RNA by organisms grown in zinc sufficient (Zn+), (Zn,+ content 1 ×10−5 M) or zinc-deficient (Zn−), (Zn+ content 1 × 10−7 M) medium. Cell division ceases on depletion of zinc from the medium. There are 20-fold less cells in (Zn−) medium than in control cultures. The size of (Zn+) cells decreases during log phase due to a reduction in the paramylon content of the cytoplasm. The size of (Zn−) cells, however, increases, due to an accumulation of paramylon. This results in a 13-fold increment in dry weight compared to control. Other cytoplasmic organelles, including Golgi bodies, mitochondria, etc. are normal. Nuclear morphology also is unchanged. There is a reduction in the rate of incorporation of labelled precursors into RNA by (Zn−) cells. The DNA content of (Zn−) E. gracilis, the absence of morphologic evidence to indicate that cell division has followed the doubling of the DNA, and the arrest in proliferation suggests that a critical zinc-dependent step in the cell cycle, localized