Transcription coordinates histone amounts and genome content

Kora-Lee Claude, Daniela Bureik, Dimitra Chatzitheodoridou, Petia Adarska, Abhyudai Singh and Kurt M. Schmoller ()
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Kora-Lee Claude: Helmholtz Zentrum München
Daniela Bureik: Helmholtz Zentrum München
Dimitra Chatzitheodoridou: Helmholtz Zentrum München
Petia Adarska: Helmholtz Zentrum München
Abhyudai Singh: University of Delaware
Kurt M. Schmoller: Helmholtz Zentrum München

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: 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 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 modeling 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.

Date: 2021
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DOI: 10.1038/s41467-021-24451-8

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