Yeast Ataxin-7 links histone deubiquitination with gene gating and mRNA export
Yeast Ataxin-7 links histone deubiquitination with gene gating and mRNA export
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DOI：
10.1038/ncb1733
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发表时间：
2008-06-01
影响因子：
21.3
通讯作者：
Hurt, Ed
中科院分区：
文献类型：
--
作者：
Koehler, Alwin;Schneider, Maren;Hurt, Ed
基因靶向核孔复合物（NPC），称为基因门控，可以影响其转录状态1 -9。然而，基因门控的机制知之甚少。在此，我们已经鉴定了SAGA相关的Sgf 73（参考文献10），人共济失调蛋白-7（参考文献11）的酵母直向同源物，作为组蛋白H2 B泛素水平的调节剂，这是一种与转录起始和延伸相关的修饰（12，13）。sgf 73是最小组蛋白去泛素化复合物的关键组分。H2 B去遍在蛋白酶Ubp 8的激活是协同的，需要与Sgf 73和Sgf 11-Sus 1的氨基末端含锌指结构域形成复合物。通过一个单独的结构域，Sgf 73介导TREX-2 mRNA输出因子Sac 3和Thp 1向佐贺的募集以及它们与Sus 1-Cdc 31的稳定相互作用。后一步对于将TREX-2靶向NPC至关重要。佐贺中Sgf 73的缺失消除了GAL 1的基因门控，并导致GAL 1 mRNA输出缺陷。因此，Sgf 73提供了一个分子支架，以整合H2 B泛素水平的调节，将基因拴系到NPC和mRNA的输出。
Targeting of a gene to the nuclear pore complexes (NPCs), known as gene gating, can affect its transcriptional state1-9. However, the mechanism underlying gene gating is poorly understood. Here, we have identified SAGA-associated Sgf73 (ref. 10), the yeast orthologue of human Ataxin-7 (ref. 11), as a regulator of histone H2B ubiquitin levels, a modification linked to both transcription initiation and elongation(12,13). Sgf73 is a key component of a minimal histone-deubiquitinating complex. Activation of the H2B deubiquitinating protease, Ubp8, is cooperative and requires complex formation with the amino-terminal zinc-finger-containing domain of Sgf73 and Sgf11-Sus1. Through a separate domain, Sgf73 mediates recruitment of the TREX-2 mRNA export factors Sac3 and Thp1 to SAGA and their stable interaction with Sus1-Cdc31. This latter step is crucial to target TREX-2 to the NPC. Loss of Sgf73 from SAGA abrogates gene gating of GAL1 and causes a GAL1 mRNA export defect. Thus, Sgf73 provides a molecular scaffold to integrate the regulation of H2B ubiquitin levels, tethering of a gene to the NPC and export of mRNA.