ELL-associated factors EAF1/2 negatively regulate HIV-1 transcription through inhibition of Super Elongation Complex formation.
EAF
ELL2
HIV-1 transcription
Super Elongation Complex
Tat
Journal
Biochimica et biophysica acta. Gene regulatory mechanisms
ISSN: 1876-4320
Titre abrégé: Biochim Biophys Acta Gene Regul Mech
Pays: Netherlands
ID NLM: 101731723
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
13
11
2019
revised:
16
02
2020
accepted:
16
02
2020
pubmed:
23
2
2020
medline:
18
7
2020
entrez:
23
2
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32087315
pii: S1874-9399(19)30416-X
doi: 10.1016/j.bbagrm.2020.194508
pii:
doi:
Substances chimiques
EAF1 protein, human
0
EAF2 protein, human
0
ELL protein, human
0
ELL2 protein, human
0
Transcription Factors
0
Transcriptional Elongation Factors
0
tat Gene Products, Human Immunodeficiency Virus
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
194508Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no conflict of interest.