Adaptive partitioning of a gene locus to the nuclear envelope in Saccharomyces cerevisiae is driven by polymer-polymer phase separation

Lidice González, Daniel Kolbin, Christian Trahan, Célia Jeronimo, François Robert, Marlene Oeffinger, Kerry Bloom and Stephen W. Michnick ()
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Lidice González: Université de Montréal
Daniel Kolbin: University of North Carolina at Chapel Hill
Christian Trahan: Institut de recherches cliniques de Montréal
Célia Jeronimo: Institut de recherches cliniques de Montréal
François Robert: Institut de recherches cliniques de Montréal
Marlene Oeffinger: Université de Montréal
Kerry Bloom: University of North Carolina at Chapel Hill
Stephen W. Michnick: Université de Montréal

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract Partitioning of active gene loci to the nuclear envelope (NE) is a mechanism by which organisms increase the speed of adaptation and metabolic robustness to fluctuating resources in the environment. In the yeast Saccharomyces cerevisiae, adaptation to nutrient depletion or other stresses, manifests as relocalization of active gene loci from nucleoplasm to the NE, resulting in more efficient transport and translation of mRNA. The mechanism by which this partitioning occurs remains a mystery. Here, we demonstrate that the yeast inositol depletion-responsive gene locus INO1 partitions to the nuclear envelope, driven by local histone acetylation-induced polymer-polymer phase separation from the nucleoplasmic phase. This demixing is consistent with recent evidence for chromatin phase separation by acetylation-mediated dissolution of multivalent histone association and fits a physical model where increased bending stiffness of acetylated chromatin polymer causes its phase separation from de-acetylated chromatin. Increased chromatin spring stiffness could explain nucleation of transcriptional machinery at active gene loci.

Date: 2023
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DOI: 10.1038/s41467-023-36391-6

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