Cell
Volume 41, Issue 2, June 1985, Pages 521-530
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A very strong enhancer is located upstream of an immediate early gene of human cytomegalovirus

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Summary

A strong transcription enhancer was identified in the genomic DNA (235 kb) of human cytomegalovirus (HCMV), a ubiquitous and severe pathogen of the herpesvirus group. Cotransfection of enhancerless SV40 DNA with randomly fragmented HCMV DNA yielded two SV40-HCMV recombinant viruses that had incorporated overlapping segments of HCMV DNA to substitute for the missing SV40 enhancer. Within HCMV, these enhancer sequences are located upstream of the transcription initiation site of the major immediate-early gene, between nucleotides -118 and −524. Deletion studies with the HCMV enhancer, which harbors a variety of repeated sequence motifs, show that different subsets of this enhancer can substitute for the SV40 enhancer. The HCMV enhancer, which seems to have little cell type or species preference, is severalfold more active than the SV40 enhancer. It is the strongest enhancer we have analyzed so far, a property that makes it a useful component of eukaryotic expression vectors.

References (72)

  • McKnightS.L. et al.

    The distal transcription signals of the herpesvirus tk gene share a common hexanucleotide control sequence

    Cell

    (1984)
  • PrestonC.M. et al.

    Effects of orientation and position on the activity of a herpes simplex virus immediate early gene farupstream region

    Virology

    (1984)
  • QueenC. et al.

    Immunoglobulin gene transcription is activated by downstream sequence elements

    Cell

    (1983)
  • VieiraJ. et al.

    The pUC plasmids, an M13mp7derived system for insertion mutagenesis and sequencing with synthetic universal primers

    Gene

    (1982)
  • WasylykB. et al.

    The SV40 72 by repeat preferentially potentiates transcription starting from proximal natural or substitute promoter elements

    Cell

    (1983)
  • WeberF. et al.

    An SV40 “enhancer trap” incorporates exogenous enhancers or generates enhancers from its own sequences

    Cell

    (1984)
  • WeberH. et al.

    Modification of the rabbit chromosomal β-globin gene by restructuring and site-directed mutagenesis

  • BenoistC. et al.

    In vivo sequence requirements of the SV40 early promoter region

    Nature

    (1981)
  • BodemerW. et al.

    Immediate-early transcription of Herpesvirus saimiri

    J. Virol.

    (1984)
  • ContrerasR. et al.

    Evidence for the direct involvement of DNA replication origin in synthesis of late SV40 RNA

    Nature

    (1982)
  • CordingleyM.G. et al.

    Functional analysis of a herpes simplex virus type 1 promoter: identification of far-upstream regulatory sequences

    Nucl. Acids Res.

    (1983)
  • de VilliersJ. et al.

    A small segment of polyoma virus DNA enhances the expression of a cloned β-globin gene over a distance of 1400 base pairs

    Nucl. Acids Res.

    (1981)
  • de VilliersJ. et al.

    Transcriptional “en hancers” from SV40 and polyoma virus show a cell type preference

    Nucl. Acids Res.

    (1982)
  • de VilliersJ. et al.

    Analysis of the transcriptional enhancer effect

  • de VilliersJ. et al.

    Polyoma virus DNA replication requires an enhancer

    Nature

    (1984)
  • EbelingA. et al.

    Genome structure and virion polypeptides of the primate herpesvirus Herpesvirus aotus types 1 and 3: comparison with human cytomegalovirus

    J. Virol.

    (1983)
  • EverettR.D. et al.

    The repeated GC-rich motifs upstream from the TATA box are important elements of the SV40 early promoter

    Nucl. Acids Res.

    (1983)
  • FriedM. et al.

    Isolation of cellular DNA sequences that allow expression of adjacent genes

  • FrommM. et al.

    Deletion mapping of DNA required for SV40 early region promoter function in vivo

    J. Mol. Appl. Genet.

    (1982)
  • GidoniD. et al.

    Multiple specific contacts between a mammalian transcription factor and its cognate promoters

    Nature

    (1984)
  • GilliesS.D. et al.

    A tissue-specific transcription enhancer element is located in the major intron of a rearranged immunoglobulin heavy chain gene

    Cell

    (1983)
  • GrussP.

    Eucaryotic enhancers

    DNA

    (1984)
  • GrussP. et al.

    Simian virus 40 repeated sequences as an element of the early promoter

  • HartzellS.W. et al.

    SV40 deletion mutants lacking the 21-bp repeated sequences are viable, but have noncomplementable deficiencies

    Nucl. Acids Res.

    (1983)
  • HenR. et al.

    An enhancer element is located 340 base pairs upstream from the adenovirus-2 ElA capsite

    Nucl. Acids Res.

    (1983)
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    Present address: Institut für Zell- und Tumorbiologie Deutsches Krebsforschungszentrum D-6900 Heidelberg Federal Republic of Germany

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