ELL-associated factors EAF1/2 negatively regulate HIV-1 transcription through inhibition of Super Elongation Complex formation.

Biochim Biophys Acta Gene Regul Mech

State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Fujian, China. Electronic address:

Published: May 2020

AI Article Synopsis

  • The ELL-containing Super Elongation Complex (SEC) is crucial for HIV-1 transactivation by the Tat protein.
  • EAF1 and EAF2 are positive regulators associated with ELL, but they inhibit HIV-1 transcription by interfering with SEC function.
  • Depleting EAF1/2 enhances SEC formation and occupancy on HIV-1 DNA, promoting Tat transactivation, indicating their role in regulating HIV-1 transcription dynamics.

Article Abstract

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.

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http://dx.doi.org/10.1016/j.bbagrm.2020.194508DOI Listing

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