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.

中文翻译：

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ELL相关因子EAF1 / 2通过抑制Super Elongation Complex的形成来负调控HIV-1转录。

含ELL（ELL1和ELL2）的超伸长复合物（SEC）是通过病毒编码的Tat蛋白有效进行HIV-1反式激活所必需的。EAF1和EAF2是ELL相关因子，被认为是ELL的正调节剂。但是，它们在HIV-1转录控制中的作用尚不清楚。在这项研究中，我们表明EAF1 / 2抑制SEC依赖性和Tat激活的HIV-1转录。发现EAF1 / 2以依赖ELL1 / 2的方式与SEC成分相互作用。令人惊讶的是，EAF1 / 2的耗尽会增加SEC的形成和在HIV-1前病毒DNA上的占有率，从而刺激HIV-1的Tat反式激活。尽管EAF1 / 2以依赖于ELL的方式与SEC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。一起，