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

Biochim Biophys Acta Gene Regul Mech. 2020 May;1863(5):194508. doi: 10.1016/j.bbagrm.2020.194508. Epub 2020 Feb 19.

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.

Keywords: EAF; ELL2; HIV-1 transcription; Super Elongation Complex; Tat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • HIV-1 / genetics*
  • HIV-1 / metabolism
  • HeLa Cells
  • Humans
  • Promoter Regions, Genetic
  • Protein Binding
  • Transcription Factors / metabolism*
  • Transcriptional Elongation Factors / metabolism
  • tat Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • EAF1 protein, human
  • EAF2 protein, human
  • ELL protein, human
  • ELL2 protein, human
  • Transcription Factors
  • Transcriptional Elongation Factors
  • tat Gene Products, Human Immunodeficiency Virus