Abstract
Chromosome architecture is essential for faithful chromosome segregation and genome stability. However, the mechanisms underlying chromosome organization are not well-characterized. Here, we identify the ubiquitin ligase Ufd4p as a master regulator of chromosome organization. Ufd4p deficiency causes longer chromosome axes and increased meiotic crossovers due to compromised condensation. Multiomics profiling reveals that Ufd4p promotes transcription of condensin components required for chromosome condensation. Mechanistically, Ufd4p targets Sum1p, a subunit of histone deacetylase complex, for proteasomal degradation. Sum1p accumulation reduces histone 4 lysine 5 acetylation, thereby suppressing condensin transcription and ultimately leading to chromosome condensation defects. Intriguingly, this pathway is shared in both meiosis and mitosis. Moreover, the mammalian homolog TRIP12 effectively rescues chromosome organization defects in
ufd4
mutants, suggesting an evolutionarily conserved mechanism. Collectively, our study elucidates an evolutionarily conserved ubiquitin–proteasome system (UPS)-dependent mechanism controlling the proper chromosome organization, highlighting the pivotal role of UPS in regulating chromosome architecture across species.