Nuclear Remodeling in Quiescent Cells: Conserved Mechanisms from Yeasts to Mammals

Quiescence is a reversible, non-proliferative cellular state that enables survival under nutrient limitation while preserving the capacity to resume growth. Rather than representing a passive default, quiescence is an actively regulated program conserved from unicellular eukaryotes to metazoans. This review focuses on the nuclear mechanisms underlying quiescence entry, maintenance, and exit, drawing on mechanistic insights from yeast models while highlighting conserved principles in multicellular systems. Across species, quiescence is characterized by global transcriptional repression, chromatin compaction, and extensive reorganization of nuclear architecture, coordinated by nutrient-sensing pathways centered on TOR/mTOR signaling. We discuss how transcriptional reprogramming is achieved through redistribution of RNA polymerases, dynamic transcription factor activities, and large-scale remodeling of histone modifications, alongside repressive chromatin formation. In parallel, post-transcriptional mechanisms—including intron retention, alternative polyadenylation, and accumulation of non-coding RNAs—fine-tune gene expression while limiting biosynthetic output. We further examine how changes in nuclear organization, such as nucleolar condensation, condensin-mediated chromosome rearrangements, and telomere hyperclusters, support long-term viability and genome stability. Collectively, this review highlights nuclear dynamics as an integrative regulatory layer that links metabolic state to cellular identity, adaptability, and long-term survival, with broad implications for development, stem cell function, and disease.