The Nucleoplasmin Homolog NLP Mediates Centromere Clustering and Anchoring to the Nucleolus
The Nucleoplasmin Homolog NLP Mediates Centromere Clustering and Anchoring to the Nucleolus
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DOI：
10.1016/j.molcel.2013.03.002
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发表时间：
2013-04-25
期刊：
影响因子：
16
通讯作者：
Heun, Patrick
中科院分区：
文献类型：
--
作者：
Padeken, Jan;Mendiburo, Maria Jose;Heun, Patrick
间期期间的着丝粒聚集是一种已知发生在许多不同生物体和细胞类型中的现象，但所涉及的因素及其生理相关性尚不清楚。利用果蝇组织培养细胞和果蝇，我们鉴定了一个蛋白质网络，包括核蓝蛋白样蛋白 (NLP)、绝缘体蛋白 CTCF 和核仁蛋白 Modulo，它们对于着丝粒的定位至关重要。人工靶向进一步证明 NLP 和 CTCF 足以进行聚类，而 Modulo 则充当核仁的锚点。研究发现着丝粒聚类依赖于中心染色质而不是特定的 DNA 序列。此外，着丝粒的散簇导致着丝粒周围异染色质组织的空间不稳定，导致重复元件沉默的部分缺陷、染色体分离过程中的缺陷和基因组不稳定。
Centromere clustering during interphase is a phenomenon known to occur in many different organisms and cell types, yet neither the factors involved nor their physiological relevance is well understood. Using Drosophila tissue culture cells and flies, we identified a network of proteins, including the nucleoplasmin-like protein (NLP), the insulator protein CTCF, and the nucleolus protein Modulo, to be essential for the positioning of centromeres. Artificial targeting further demonstrated that NLP and CTCF are sufficient for clustering, while Modulo serves as the anchor to the nucleolus. Centromere clustering was found to depend on centric chromatin rather than specific DNA sequences. Moreover, unclustering of centromeres results in the spatial destabilization of pericentric heterochromatin organization, leading to partial defects in the silencing of repetitive elements, defects during chromosome segregation, and genome instability.