The promoter activity of long terminal repeats of the HERV-H family of human retrovirus-like elements is critically dependent on Sp1 family proteins interacting with a GC/GT box located immediately 3' to the TATA box.
The HERV-H family of endogenous retrovirus-like elements is widely distributed in the human genome, with about 1,000 full-length elements and a similar number of solitary long terminal repeats (LTRs). HERV-H LTRs have been shown to direct the transcription of both HERV-H-encoded and adjacent cellular genes. Transcripts of HERV-H elements are especially abundant in placenta, teratocarcinoma cell lines, and cell lines derived from testicular and lung tumors. Here we report that only a subset of HERV-H LTRs display promoter activity in human cell lines and that these LTRs are characterized by the presence of a GC/GT box immediately downstream of the TATA box. This GC/GT box is required for promoter activity, while, surprisingly, the TATA box is dispensable. The ubiquitously expressed transcription factors Sp1 and Sp3 bound to this GC/GT box and stimulated transcription from the promoter-active LTRs in the teratocarcinoma cell line NTera2-D1. However, in HeLa and Drosophila SL-2 cells, Sp1 acted as a transcriptional activator of the LTRs, while Sp3 acted as a repressor of Sp1-mediated transcriptional activation. Cotransfection studies also revealed that the tissue-specific Sp1-related protein BTEB bound to this GC/GT box and stimulated transcription from the LTR promoters in NTera2-D1 cells. These results show that members of the Sp1 protein family are crucial determinants for transcriptional activation of HERV-H LTR promoters and suggest that these proteins may also be involved in determining the tissue-specific expression pattern of HERV-H elements.
Sjøttem
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Department of Biochemistry, Institute of Medical Biology, University of Tromsø, Norway.
Anderssen
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Johansen
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D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D003596:Cytosine / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D006147:Guanine / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D012190:Retroviridae / Q000235:genetics*; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D051705:Sp3 Transcription Factor; D016385:TATA Box; D013941:Thymine / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D004279:DNA, Viral; D004268:DNA-Binding Proteins; C489676:KLF9 protein, human; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; C497121:SP3 protein, human; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D051705:Sp3 Transcription Factor; D006147:Guanine; D003596:Cytosine; D013941:Thymine