Transcriptional activation of the human T-lymphotropic virus type I long terminal repeat by functional interaction of Tax1 and Ets1.
Transcription regulation of the oncogenic retrovirus human T-lymphotropic virus type I (HTLV-I) involves the composite activity of both viral and cellular transcription factors. The HTLV-I transforming protein, Tax1, modulates the activity of several cellular transcription factors, upregulating the level of viral gene expression. In addition, cellular transcription factors, such as Ets1, independently bind to the viral long terminal repeat in a sequence-specific manner and activate transcription. It was of interest to analyze the possible interaction of Tax1 and Ets1 in viral gene regulation. We now report that Tax1 and Ets1 increase expression from the HTLV-I promoter in a cooperative manner. The level of expression was increased 5- to 10-fold above the combined individual effect of Tax1 and Ets1. S1 nuclease analysis demonstrated that the cooperative effect was due to an increase in the levels of steady-state RNA. The functional interaction between Tax1 and Ets1 required the presence of the Tax1-responsive 21-bp repeat element TRE-1 and the Ets1-responsive element ERR-1. These results suggested the possible interaction of Ets1 with transcriptional regulatory proteins that bind to the 21-bp repeats. This interaction is demonstrated by decreased electrophoretic mobility of specific 21-bp repeat gel shift complexes in the presence of Ets1. Furthermore, interaction of Ets1 with the 21-bp repeat-binding proteins enhances the relative efficiency of binding to the DNA. This cooperative interaction between Ets1 and proteins which bind to the Tax1-responsive 21-bp repeats suggests a possible role for Ets1 in the regulation of viral gene expression.
Gitlin
S D
SD
Laboratory of Molecular Virology, National Cancer Institute, Bethesda, Maryland 20892.
Dittmer
J
J
Shin
R C
RC
Brady
J N
JN
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase; D004591:Electrophoresis, Polyacrylamide Gel; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000378:metabolism*; D017930:Genes, Reporter; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D008969:Molecular Sequence Data; D009036:Moths; D011401:Promoter Regions, Genetic / Q000235:genetics; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D012367:RNA, Viral / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D015719:Single-Strand Specific DNA and RNA Endonucleases / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection
C494041:ETS1 protein, human; D016356:Gene Products, tax; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012367:RNA, Viral; D014157:Transcription Factors; D015500:Chloramphenicol O-Acetyltransferase; D015719:Single-Strand Specific DNA and RNA Endonucleases