State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Fujian, China.
State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Fujian, China.
Biochim Biophys Acta Gene Regul Mech. 2020 May;1863(5):194508. doi: 10.1016/j.bbagrm.2020.194508. Epub 2020 Feb 19.
The ELL (ELL1 and ELL2)-containing Super Elongation Complex (SEC) is required for efficient HIV-1 transactivation by the viral-encoded Tat protein. EAF1 and EAF2 are ELL-associated factors and considered as positive regulators of ELL. However, their role in HIV-1 transcriptional control is unknown. In this study, we show that EAF1/2 inhibit the SEC-dependent and Tat-activated HIV-1 transcription. EAF1/2 are found to interact with the SEC components in an ELL1/2-dependent manner. Surprisingly, the depletion of EAF1/2 increases the SEC formation and occupancy on the HIV-1 proviral DNA, thereby stimulating Tat transactivation of HIV-1. Although EAF1/2 interact with members of the SEC in a ELL-dependent manner, this interaction competes with the binding of the scaffolding subunit AFF1 with ELL, thus reducing the SEC formation. Together, these data reveal how EAF1/2 regulate the SEC formation to control HIV-1 transcription.
ELL（ELL1 和 ELL2）包含的超延伸复合物（SEC）是 HIV-1 病毒编码的 Tat 蛋白进行有效转录激活所必需的。EAF1 和 EAF2 是 ELL 相关因子，被认为是 ELL 的正向调节因子。然而，它们在 HIV-1 转录控制中的作用尚不清楚。在本研究中，我们表明 EAF1/2 抑制 SEC 依赖和 Tat 激活的 HIV-1 转录。发现 EAF1/2 以 ELL1/2 依赖的方式与 SEC 成分相互作用。令人惊讶的是，EAF1/2 的耗竭增加了 SEC 在 HIV-1 前病毒 DNA 上的形成和占据，从而刺激了 HIV-1 的 Tat 转录激活。尽管 EAF1/2 以 ELL 依赖的方式与 SEC 的成员相互作用，但这种相互作用与支架亚基 AFF1 与 ELL 的结合竞争，从而减少了 SEC 的形成。总之，这些数据揭示了 EAF1/2 如何调节 SEC 的形成来控制 HIV-1 转录。
