Cucinotta Christine, Dell Rachel, Alavattam Kris, Tsukiyama Toshio
Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Department of Molecular Genetics, Ohio State University, Columbus, OH, 43210, USA.
bioRxiv. 2024 Dec 12:2024.12.12.628092. doi: 10.1101/2024.12.12.628092.
Quiescence in is a reversible G crucial for long-term survival under nutrient-deprived conditions. During quiescence, the genome is hypoacetylated and chromatin undergoes significant compaction. However, the 3D structure of the ribosomal DNA (rDNA) locus in this state is not well understood. Here, we report that the rDNA locus in quiescent cells forms a distinct condensed loop-like structure, different from structures observed during the mitotic cell cycle. Deletion of disrupts this structure, causing it to collapse into a small dot and resulting in quiescence entry and exit defects. In contrast, Sir2 affects rDNA structure only modestly in G2/M phase. In the absence of Sir2, occupancy of both RNA Polymerase II and histone H3 increase at the rDNA locus during quiescence and through quiescence exit, further indicating gross defects in chromatin structure. Together, these results uncover a previously undescribed rDNA chromatin structure specific to quiescent cells and underscore the importance of Sir2 in facilitating the transition between cellular states.
静止状态是细胞在营养缺乏条件下长期存活所必需的一种可逆的G状态。在静止期间，基因组发生低乙酰化，染色质经历显著压缩。然而，这种状态下核糖体DNA（rDNA）位点的三维结构尚不清楚。在此，我们报告静止细胞中的rDNA位点形成一种独特的浓缩环状结构，不同于有丝分裂细胞周期中观察到的结构。删除[相关基因]会破坏这种结构，使其坍塌成一个小点，并导致静止进入和退出缺陷。相比之下，Sir2在G2/M期对rDNA结构的影响较小。在没有Sir2的情况下，RNA聚合酶II和组蛋白H3在静止期间以及静止退出过程中在rDNA位点的占据增加，进一步表明染色质结构存在严重缺陷。总之，这些结果揭示了一种以前未描述的静止细胞特有的rDNA染色质结构，并强调了Sir2在促进细胞状态转变中的重要性。
