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

J Virol. 1996 Jan;70(1):188-98. doi: 10.1128/JVI.70.1.188-198.1996.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Cytosine / metabolism
  • DNA, Viral / genetics
  • DNA, Viral / metabolism
  • DNA-Binding Proteins / metabolism
  • Enhancer Elements, Genetic
  • Guanine / metabolism
  • HeLa Cells
  • Humans
  • Kruppel-Like Transcription Factors
  • Molecular Sequence Data
  • Nuclear Proteins / metabolism
  • Promoter Regions, Genetic*
  • Repetitive Sequences, Nucleic Acid / genetics*
  • Retroviridae / genetics*
  • Sp1 Transcription Factor / metabolism*
  • Sp3 Transcription Factor
  • TATA Box*
  • Thymine / metabolism
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Tumor Cells, Cultured


  • DNA, Viral
  • DNA-Binding Proteins
  • KLF9 protein, human
  • Kruppel-Like Transcription Factors
  • Nuclear Proteins
  • SP3 protein, human
  • Sp1 Transcription Factor
  • Transcription Factors
  • Sp3 Transcription Factor
  • Guanine
  • Cytosine
  • Thymine

Associated data

  • GENBANK/U95997
  • GENBANK/U95998
  • GENBANK/U95999
  • GENBANK/U96000
  • GENBANK/U96001
  • GENBANK/U96002
  • GENBANK/U96003
  • GENBANK/U96004