Nucleoporins Directly Stimulate Expression of Developmental and Cell-Cycle Genes Inside the Nucleoplasm
Nucleoporins Directly Stimulate Expression of Developmental and Cell-Cycle Genes Inside the Nucleoplasm
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DOI：
10.1016/j.cell.2010.01.011
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发表时间：
2010-02-05
期刊：
影响因子：
64.5
通讯作者：
Fornerod, Maarten
中科院分区：
文献类型：
--
作者：
Kalverda, Bernike;Pickersgill, Helen;Fornerod, Maarten
核孔复合体（NPCs）介导穿过核膜的运输。在酵母中，它们还与活性基因相互作用，将其吸引或保留在核周边。在高等真核生物中，一些核孔复合体成分（核孔蛋白）也存在于核质中，其功能至今未知。我们对果蝇中特别是在核孔复合体处或核质内的核孔蛋白 - 染色质相互作用进行了功能特性分析。我们分析了全长核孔蛋白Nup98、Nup50和Nup62以及核质和核孔复合体连接形式的Nup98的基因组相互作用。我们发现核孔蛋白主要与核质内转录活跃的基因相互作用，特别是那些参与发育调控和细胞周期的基因。一小部分非活性基因与核孔复合体相互作用。与核质Nup98强烈相互作用的基因在Nup98缺失时下调，在核质Nup98过表达时激活。因此，核孔蛋白通过在核质内与这些基因相互作用，在远离核孔复合体的位置刺激发育和细胞周期基因的表达。
Nuclear pore complexes (NPCs) mediate transport across the nuclear envelope. In yeast, they also interact with active genes, attracting or retaining them at the nuclear periphery. In higher eukaryotes, some NPC components (nucleoporins) are also found in the nucleoplasm, with a so far unknown function. We have functionally characterized nucleoporin-chromatin interactions specifically at the NPC or within the nucleoplasm in Drosophila. We analyzed genomic interactions of full-length nucleoporins Nup98, Nup50, and Nup62 and nucleoplasmic and NPC-tethered forms of Nup98. We found that nucleoporins predominantly interacted with transcriptionally active genes inside the nucleoplasm, in particular those involved in developmental regulation and the cell cycle. A smaller set of nonactive genes interacted with the NPC. Genes strongly interacting with nucleoplasmic Nup98 were downregulated upon Nup98 depletion and activated on nucleoplasmic Nup98 overexpression. Thus, nucleoporins stimulate developmental and cell-cycle gene expression away from the NPC by interacting with these genes inside the nucleoplasm.