Biochemistry and Biophysics Department, University of California, San Francisco, San Francisco, CA 94158, USA.
J Cell Biol. 2010 Feb 22;188(4):491-503. doi: 10.1083/jcb.200908026.
In an RNA interference screen interrogating regulators of mouse embryonic stem (ES) cell chromatin structure, we previously identified 62 genes required for ES cell viability. Among these 62 genes were Smc2 and -4, which are core components of the two mammalian condensin complexes. In this study, we show that for Smc2 and -4, as well as an additional 49 of the 62 genes, knockdown (KD) in somatic cells had minimal effects on proliferation or viability. Upon KD, Smc2 and -4 exhibited two phenotypes that were unique to ES cells and unique among the ES cell-lethal targets: metaphase arrest and greatly enlarged interphase nuclei. Nuclear enlargement in condensin KD ES cells was caused by a defect in chromatin compaction rather than changes in DNA content. The altered compaction coincided with alterations in the abundance of several epigenetic modifications. These data reveal a unique role for condensin complexes in interphase chromatin compaction in ES cells.
在一项针对调控小鼠胚胎干细胞 (ES) 细胞染色质结构的 RNA 干扰筛选实验中，我们先前鉴定出 62 个维持 ES 细胞活力所必需的基因。这 62 个基因中包括 Smc2 和 -4，它们是两种哺乳动物凝聚素复合物的核心组成部分。在这项研究中，我们发现对于 Smc2 和 -4，以及另外 49 个 62 个基因中的基因，体细胞中的敲低 (KD) 对增殖或活力几乎没有影响。在 KD 后，Smc2 和 -4 表现出两种表型，这两种表型仅存在于 ES 细胞中，并且在 ES 细胞致死靶标中是独特的：中期停滞和间期核明显增大。凝聚素 KD ES 细胞中的核增大是由染色质紧缩缺陷引起的，而不是 DNA 含量的变化。这种改变的紧缩与几种表观遗传修饰的丰度改变相一致。这些数据揭示了凝聚素复合物在 ES 细胞间期染色质紧缩中的独特作用。
Zotero 插件
