Abstract
PA28γ, a nuclear activator of the 20S proteasome, is involved in the degradation of several proteins regulating cell proliferation, but its precise cellular functions remain unclear. Here, we show that PA28γ is crucial for chromatin compaction. In human cells, we find that a small fraction of PA28γ co-localizes with HP1β, and PA28γ is present at HP1β-containing repetitive-DNA regions. PA28γ-depletion induces a decompaction of pericentromeric heterochromatin, as observed upon HP1β-knockdown. Using a quantitative FLIM-FRET based microscopy assay monitoring close proximity between nucleosomes in living cells, we show that PA28γ controls chromatin compaction more broadly. Importantly, HP1β on its own is unable to drive chromatin compaction without the presence of PA28γ. At the molecular level, PA28γ is necessary to maintain the level of H3K9 tri-methylation, as well as H4K20 mono- and tri-methylation, modifications required for heterochromatin establishment. Overall, our findings demonstrate the implication of a proteasome regulator in chromatin organization.