HIV-1 tat binds TAFII250 and represses TAFII250-dependent transcription of major histocompatibility class I genes.
HIV Tat, a transactivator of viral transcription, represses transcription of major histocompatibility (MHC) class I genes. Repression depends exclusively on the C-terminal domain of Tat, although the mechanism of this repression has not been known. We now show that repression results from the interaction of Tat with the TAFII250 component of the general transcription factor, TFIID. The C-terminal domain of Tat binds to a site on TAFII250 that overlaps the histone acetyl transferase domain, inhibiting TAFII250 histone acetyl transferase activity. Furthermore, promoters repressed by Tat, including the MHC class I promoter, are dependent on TAFII250 whereas those that are not repressed by Tat, such as SV40 and MuLV promoters, are independent of functional TAFII250. Thus, Tat repression of MHC class I transcription would be one mechanism by which HIV avoids immune surveillance.
Weissman
J D
JD
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Brown
J A
JA
Howcroft
T K
TK
Hwang
J
J
Chawla
A
A
Roche
P A
PA
Schiltz
L
L
Nakatani
Y
Y
Singer
D S
DS
D000123:Acetyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D006224:Cricetinae; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism*; D005805:Genes, MHC Class I; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID; D054322:tat Gene Products, Human Immunodeficiency Virus
D017931:DNA Primers; D004268:DNA-Binding Proteins; D015696:Gene Products, tat; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID; D054322:tat Gene Products, Human Immunodeficiency Virus; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C069001:TATA-binding protein associated factor 250 kDa