Protein Tpr is required for establishing nuclear pore-associated zones of heterochromatin exclusion.

Protein Tpr is required for establishing nuclear pore-associated zones of heterochromatin exclusion.
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DOI:
10.1038/emboj.2010.54
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发表时间:
2010-05-19
期刊:
影响因子:
11.4
通讯作者:
Cordes, Volker C.
Cordes, Volker C.
中科院分区:
生物学1区
文献类型:
--
作者:
Krull, Sandra;Doerries, Julia;Boysen, Bjoern;Reidenbach, Sonja;Magnius, Lars;Norder, Helene;Thyberg, Johan;Cordes, Volker C.

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体细胞中的异染色质聚集与核膜(NE)紧密接触,但被通道状和锥状区域间隔开,这些区域似乎基本没有异染色质且与核孔复合体(NPCs)相关。为了鉴定参与形成这种异染色质排斥区(HEZs)的蛋白质,我们使用了一种细胞培养模型,其中脊髓灰质炎病毒(PV)感染诱导的染色质凝聚显示出与正常组织细胞中相似的HEZs。HEZ的出现依赖于与NPC相关的蛋白Tpr及其形成大的卷曲螺旋结构域。RNA干扰介导的Tpr缺失使得凝聚的染色质沿着NE的核表面各处出现,导致HEZs不再形成,并且NPCs被异染色质覆盖。这些结果表明Tpr作为核周组织的决定因素具有核心功能,在形成形态上独特的核亚区室以及界定异染色质分布方面具有直接作用。
Amassments of heterochromatin in somatic cells occur in close contact with the nuclear envelope (NE) but are gapped by channel- and cone-like zones that appear largely free of heterochromatin and associated with the nuclear pore complexes (NPCs). To identify proteins involved in forming such heterochromatin exclusion zones (HEZs), we used a cell culture model in which chromatin condensation induced by poliovirus (PV) infection revealed HEZs resembling those in normal tissue cells. HEZ occurrence depended on the NPC-associated protein Tpr and its large coiled coil-forming domain. RNAi-mediated loss of Tpr allowed condensing chromatin to occur all along the NE's nuclear surface, resulting in HEZs no longer being established and NPCs covered by heterochromatin. These results assign a central function to Tpr as a determinant of perinuclear organization, with a direct role in forming a morphologically distinct nuclear sub-compartment and delimiting heterochromatin distribution.
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