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

ABSTRACT: Partitioning of active gene loci to the nuclear envelope is a key mechanism by which organisms can increase the speed of adaptation and metabolic robustness to fluctuating resources in the environment. In the budding yeast Saccharomyces cerevisiae, adaptation and transcriptional memory induced by nutrient depletion or other stresses, results from relocalization of active gene loci from nucleoplasm to the nuclear envelope, leading to increased transport of mRNAs to the cytosol and their translation. The mechanism by which this translocation occurs remains a mystery. We show here, that for the inositol depletion-responsive gene locus INO1 in yeast, translocation to the nuclear envelope is caused by a local phase transition of the mechanical stiffness of chromatin surrounding activated INO1 that favors phase separation of the active gene locus into low density regions of chromatin proximal to the nuclear envelope. Gene regulatory elements essential to translocation encode binding sites for histone acetyl transferases, which are necessary for chromatin decompaction. INO1 locus partitioning can be explained by a phenomenological model of chromatin decompaction, which reflects stiffening of chromatin and its partitioning into a dilute chromatin phase adjacent to the nuclear envelope, from the dense chromatin found in the nucleoplasmic phase. Recent evidence suggests that this demixing of chromatin could be due to the dissolution of multivalent chromatin interactions mediated by histone post-translational modifications.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: Marlene Oeffinger  

LAB HEAD: Marlene Eloise Oeffinger

PROVIDER: PXD029913 | Pride | 2023-03-01

REPOSITORIES: Pride