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首页> 外文期刊>Molecular and Cellular Biology >Differential Properties of Transcriptional Complexes Formed by the CoREST Family
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Differential Properties of Transcriptional Complexes Formed by the CoREST Family

机译：CoREST家族形成的转录复合物的差异性质

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Mammalian genomes harbor three CoREST genes. rcor1 encodes CoREST (CoREST1), and the paralogues rcor2 and rcor3 encode CoREST2 and CoREST3, respectively. Here, we describe specific properties of transcriptional complexes formed by CoREST proteins with the histone demethylase LSD1/KDM1A and histone deacetylases 1 and 2 (HDAC1/2) and the finding that all three CoRESTs are expressed in the adult rat brain. CoRESTs interact equally strongly with LSD1/KDM1A. Structural analysis shows that the overall conformation of CoREST3 is similar to that of CoREST1 complexed with LSD1/KDM1A. Nonetheless, transcriptional repressive capacity of CoREST3 is lower than that of CoREST1, which correlates with the observation that CoREST3 leads to a reduced LSD1/KDM1A catalytic efficiency. Also, CoREST2 shows a lower transcriptional repression than CoREST1, which is resistant to HDAC inhibitors. CoREST2 displays lower interaction with HDAC1/2, which is barely present in LSD1/KDM1A-CoREST2 complexes. A nonconserved leucine in the first SANT domain of CoREST2 severely weakens its association with HDAC1/2. Furthermore, CoREST2 mutants with increased HDAC1/2 interaction and those without HDAC1/2 interaction exhibit equivalent transcriptional repression capacities, indicating that CoREST2 represses in an HDAC-independent manner. In conclusion, differences among CoREST proteins are instrumental in the modulation of protein-protein interactions and catalytic activities of LSD1/KDM1A-CoREST-HDAC complexes, fine-tuning gene expression regulation.
机译：哺乳动物基因组包含三个CoREST基因。 rcor1 对CoREST（CoREST1）进行编码，而对等物 rcor2 和 rcor3 分别对CoREST2和CoREST3进行编码。在这里，我们描述了由CoREST蛋白与组蛋白脱甲基酶LSD1 / KDM1A和组蛋白脱乙酰基酶1和2（HDAC1 / 2）形成的转录复合物的特定特性，以及发现所有三种CoREST在成年大鼠脑中表达的发现。 CoREST与LSD1 / KDM1A具有同等强大的交互作用。结构分析表明，CoREST3的总体构象与与LSD1 / KDM1A复杂的CoREST1的构象相似。尽管如此，CoREST3的转录抑制能力低于CoREST1的转录抑制能力，这与CoREST3导致LSD1 / KDM1A催化效率降低的观察结果相关。同样，CoREST2显示出比CoREST1低的转录抑制，而CoREST1对HDAC抑制剂具有抗性。 CoREST2与HDAC1 / 2的交互作用较低，而HDAC1 / 2在LSD1 / KDM1A-CoREST2复合物中几乎不存在。 CoREST2的第一个SANT域中的非保守亮氨酸会严重削弱其与HDAC1 / 2的关联。此外，具有增加的HDAC1 / 2相互作用的CoREST2突变体和没有HDAC1 / 2相互作用的CoREST2突变体表现出同等的转录抑制能力，表明CoREST2以HDAC独立的方式抑制。总之，CoREST蛋白质之间的差异有助于调节LSD1 / KDM1A-CoREST-HDAC复合物的蛋白质-蛋白质相互作用和催化活性，从而微调基因表达调控。

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