Negative cofactor 2 (NC2), including two subunits NC2α and NC2β, 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 NC2α–NC2β 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 NC2β 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.

中文翻译：

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NC2复合物是通过调节H2A.Z沉积来激活过氧化氢酶3转录的关键因素。

负辅助因子2（NC2），包括两个亚基NC2α和NC2β，是真核生物中II类基因转录的保守正/负调节剂。已知NC2通过调节转录预起始复合物的组装而起作用。但是，尚不清楚NC2在转录调控中的确切作用。在这里，我们揭示了在神经孢霉中，NC2以两个亚基的组蛋白折叠（HF）域介导的异二聚体形式激活过氧化氢酶3（cat-3）基因转录。两个亚基中任一亚基的HF结构域的缺失都会破坏NC2α–NC2β的相互作用，并破坏完整的NC2异二聚体与cat-3基因座的结合。NC2的丢失显着增加了cat-3上的组蛋白变异H2A.Z沉积轨迹。进一步的研究表明，NC2募集染色质重塑复合物INO80C以从cat-3基因座周围的核小体中去除H2A.Z ，从而导致cat-3的转录激活。有趣的是，除了两个亚基的HF域外，NC2β的C末端阻遏域不仅是NC2与cat-3基因座的结合所必需的，而且还需要将INO80C募集到cat-3基因座上，并从核小体中去除H2A.Z。。总的来说，我们的发现揭示了通过募集INO80C从含有H2A.Z的特殊核小体中去除H2A.Z的新机制，即NC2在转录激活中的作用。