Human T cell transcription factor GATA-3 stimulates HIV-1 expression

Z Yang, JD Engel - Nucleic acids research, 1993 - academic.oup.com
Z Yang, JD Engel
Nucleic acids research, 1993academic.oup.com
A family of transcriptional activating proteins, the GATA factors, has been shown to bind to a
consensus motif through a highly conserved C4 zinc finger DNA binding domain. One
member of this multigene family, GATA-3, is most abundantly expressed in T lymphocytes, a
cellular target for human immunodeficiency virus type 1 (HIV-1) infection and replication. In
vitro DNase I footprinting analysis revealed six hGATA-3 binding sites in the U3 region (the
transcriptional regulatory domain) of the HIV-1 LTR. Cotransfection of an hGATA-3 …
Abstract
A family of transcriptional activating proteins, the GATA factors, has been shown to bind to a consensus motif through a highly conserved C4 zinc finger DNA binding domain. One member of this multigene family, GATA-3, is most abundantly expressed in T lymphocytes, a cellular target for human immunodeficiency virus type 1 (HIV-1) infection and replication. In vitro DNase I footprinting analysis revealed six hGATA-3 binding sites in the U3 region (the transcriptional regulatory domain) of the HIV-1 LTR. Cotransfection of an hGATA-3 expression plasmid with a reporter plasmid whose transcription is directed by the HIV-1 LTR resulted in 6- to 10-fold stimulation of LTR-medlated transcription, whereas site specific mutation of these GATA sites resulted In virtual abrogation of the activation by hGATA-3. Further, deletion of the hGATA-3 transcriptional activation domain abolished GATA-dependent HIV-1 trans-activation, showing that the stimulation of viral transcription observed is a direct effect of cotransfected hGATA-3. Introduction of the HIV-1 plasmids in which the GATA sites have been mutated into human T lymphocytes also caused a significant reduction In LTR-mediated transcription at both the basal level and in (PHA- plus PMA-) stimulated T cells. These observations suggest that in addition to its normal role in T lymphocyte gene regulation, hGATA-3 may also play a significant role in HIV-1 transcriptional activation.
Oxford University Press