NC2 complex is a key factor for the activation of catalase-3 transcription by regulating H2A.Z deposition
NC2 complex is a key factor for the activation of catalase-3 transcription by regulating H2A.Z deposition
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NC2 复合物是通过调节 H2A.Z 沉积激活过氧化氢酶 3 转录的关键因素
DOI：
10.1093/nar/gkaa552
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发表时间：
2020-09-04
影响因子：
14.9
通讯作者：
He, Qun
中科院分区：
文献类型：
--
作者：
Cui, Guofei;Dong, Qing;He, Qun
负辅因子2（negative cofactor 2，NC 2）是真核生物II类基因转录的一个保守的正/负调控因子，包括NC 2 α和NC 2 β两个亚基。已知NC 2通过调节转录前起始复合物的组装来发挥功能。然而，NC 2在转录调控中的确切作用仍不清楚。在这里，我们发现，在粗糙脉孢菌，NC 2激活过氧化氢酶-3（cat-3）基因转录的异源二聚体的形式介导的组蛋白折叠（HF）结构域的两个亚基。两个亚基中任一个中的HF结构域的缺失破坏了NC 2 α-NC 2 β相互作用和完整NC 2异二聚体与cat-3基因座的结合。NC 2的缺失显著增加组蛋白变体H2A.Z在cat-3位点的沉积。进一步的研究表明，NC 2募集染色质重塑复合物INO 80 C从cat-3基因座周围的核小体中去除H2 A. Z，导致cat-3的转录激活。除了两个亚基的HF结构域之外，有趣的是，NC 2 β的C-末端抑制结构域不仅对于NC 2与cat-3位点的结合是必需的，而且对于INO 80 C向cat-3位点的募集和H2A.Z从核小体的去除也是必需的。总的来说，我们的研究结果揭示了一种新的机制，NC 2在转录激活通过招募INO 80 C，以消除H2 A. Z从特殊的含H2 A. Z的核小体。
Negative cofactor 2 (NC2), including two subunits NC2 alpha and NC2 beta, is a conserved positive/negative regulator of class II gene transcription in eukaryotes. It is known that NC2 functions by regulating the assembly of the transcription preinitiation complex. However, the exact role of NC2 in transcriptional regulation is still unclear. Here, we reveal that, in Neurospora crassa, NC2 activates catalase-3 (cat-3) gene transcription in the form of heterodimer mediated by histone fold (HF) domains of two subunits. Deletion of HF domain in either of two subunits disrupts the NC2 alpha-NC2 beta interaction and the binding of intact NC2 heterodimer to cat-3 locus. Loss of NC2 dramatically increases histone variant H2A.Z deposition at cat-3 locus. Further studies show that NC2 recruits chromatin remodeling complex INO80C to remove H2A.Z from the nucleosomes around cat-3 locus, resulting in transcriptional activation of cat-3. Besides HF domains of two subunits, interestingly, C-terminal repression domain of NC2 beta is required not only for NC2 binding to cat-3 locus, but also for the recruitment of INO80C to cat-3 locus and removal of H2A.Z from the nucleosomes. Collectively, our findings reveal a novel mechanism of NC2 in transcription activation through recruiting INO80C to remove H2A.Z from special H2A.Z-containing nucleosomes.