Changing growth conditions prompt large-scale rearrangements of budding yeast chromosomes, Dultz et al. reveal.
Genes can change their position within the nucleus when they are activated or repressed. The GAL locus on budding yeast chromosome II, for example, is transcriptionally activated and relocated to the nuclear periphery when glucose in the cells’ growth medium is replaced with galactose. Whether the repositioning of individual genes is accompanied by larger scale changes in chromosome organization is unclear, however, so Dultz et al. developed an automated imaging protocol to analyze how the location of different, fluorescently labeled chromosome regions changed under varying growth conditions.
Glucose withdrawal induced the relocation of not just the GAL locus but also many additional regions of chromosome II to the nuclear periphery. Loci on other chromosomes also moved to the nuclear envelope in the absence of glucose. Computer modeling combined with experimental analyses showed that this global chromatin reorganization depends on several tethering sites located throughout the yeast genome.
To understand how the nuclear position of these sites might be regulated, Dultz et al. conducted a genetic screen for mutants affecting GAL repositioning. The screen identified several components of histone deacetylase complexes; deleting these genes or inhibiting deacetylase activity with the drug trichostatin A blocked the relocalization of GAL and other chromosomal loci to the nuclear periphery. The histone acetyl transferase activity of the SAGA complex was also required for global chromatin reorganization in response to changing carbon availability. Dultz and colleagues note that the targets of these enzymes, and the functional consequence of blocking chromatin rearrangements, remain unclear.
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