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Cooperative interaction of Ets‐1 with USF‐1 required for HIV‐1 enhancer activity in T cells
Author(s) -
Sieweke Michael H.,
Tekotte Hildegard,
Jarosch Ursula,
Graf Thomas
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.6.1728
Subject(s) - biology , enhancer , human immunodeficiency virus (hiv) , genetics , computational biology , microbiology and biotechnology , virology , transcription factor , gene
The distal enhancer region of the human immunodeficiency virus 1 (HIV‐1) long terminal repeat (LTR) is known to be essential for HIV replication and to contain immediately adjacent E‐box and Ets binding sites. Based on a yeast one‐hybrid screen we have identified the E‐box binding protein USF‐1 as a direct interaction partner of Ets‐1 and found that the complex acts on this enhancer element. The binding surfaces of USF‐1 and Ets‐1 map to their DNA‐binding domains and although these domains are highly conserved, the interaction is very selective within the respective protein family. USF‐1 and Ets‐1 synergize in specific DNA binding as well as in the transactivation of reporter constructs containing the enhancer element, and mutations of the individual binding sites dramatically reduce reporter activity in T cells. In addition, a dominant negative Ets‐1 mutant inhibits both USF‐1‐mediated transactivation and the activity of the HIV‐1 LTR in T cells. The inhibition is independent of Ets DNA‐binding sites but requires the Ets binding surface on USF‐1, highlighting the importance of the direct protein–protein interaction. Together these results indicate that the interaction between Ets‐1 and USF‐1 is required for full transcriptional activity of the HIV‐1 LTR in T cells.