Condensin-Dependent Chromatin Compaction Represses Transcription Globally during Quiescence
Condensin-Dependent Chromatin Compaction Represses Transcription Globally during Quiescence
复制标题
DOI：
10.1016/j.molcel.2018.11.020
复制
发表时间：
2019-02-07
期刊：
影响因子：
16
通讯作者：
Tsukiyama, Toshio
中科院分区：
文献类型：
--
作者：
Swygert, Sarah G.;Kim, Seungsoo;Tsukiyama, Toshio
静止是一种抗压状态，在这种状态下，细胞可逆地退出细胞周期，并暂停大多数过程。静止对于干细胞的维持是必不可少的，而它的错误调节与肿瘤的形成有关。静止细胞的特征之一是高度浓缩的染色质。因为浓缩的染色质经常与转录沉默相关，所以人们假设染色质的压缩在静止时抑制转录。然而，以前还没有通过在基因分辨率下确定细胞内染色质结构来测试这一模型的技术。在这里，我们使用Micro-C XL在全基因组范围内以单核小体分辨率定位静止的酿酒酵母细胞中的染色质接触。我们描述了染色质结构域，大约10-60千碱基，只有在静止的细胞中，才是由凝集素介导的环形成的。凝集素耗尽阻止染色质在结构域内的紧凑，并导致广泛的转录抑制。最后，我们证明了凝集素依赖的染色质压缩在静止的人成纤维细胞中是保守的。
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.