Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Mol Cell. 2019 Feb 7;73(3):533-546.e4. doi: 10.1016/j.molcel.2018.11.020. Epub 2018 Dec 27.
Quiescence is a stress-resistant state in which cells reversibly exit the cell cycle and suspend most processes. Quiescence is essential for stem cell maintenance, and its misregulation is implicated in tumor formation. One of the hallmarks of quiescent cells is highly condensed chromatin. Because condensed chromatin often correlates with transcriptional silencing, it has been hypothesized that chromatin compaction represses transcription during quiescence. However, the technology to test this model by determining chromatin structure within cells at gene resolution has not previously been available. Here, we use Micro-C XL to map chromatin contacts at single-nucleosome resolution genome-wide in quiescent Saccharomyces cerevisiae cells. We describe chromatin domains on the order of 10-60 kilobases that, only in quiescent cells, are formed by condensin-mediated loops. Condensin depletion prevents the compaction of chromatin within domains and leads to widespread transcriptional de-repression. Finally, we demonstrate that condensin-dependent chromatin compaction is conserved in quiescent human fibroblasts.
静止是一种抗应激状态,在此状态下细胞可逆地退出细胞周期并暂停大多数进程。静止对于干细胞维持至关重要,其失调与肿瘤形成有关。静止细胞的特征之一是染色质高度浓缩。由于浓缩的染色质通常与转录沉默相关,因此人们假设染色质紧缩在静止期间抑制转录。然而,以前没有可用的技术通过确定细胞内基因分辨率的染色质结构来测试该模型。在这里,我们使用 Micro-C XL 在静止的酿酒酵母细胞中以单核小体分辨率全基因组范围绘制染色质接触图。我们描述了大约 10-60 千碱基的染色质域,这些域仅在静止细胞中,由凝聚素介导的环形成。凝聚素耗竭可防止域内染色质的紧缩,并导致广泛的转录去阻遏。最后,我们证明了在静止的人成纤维细胞中,凝聚素依赖性染色质紧缩是保守的。