The Journal of Immunology, Vol 151, Issue 11 6099-6109, Copyright © 1993 by American Association of Immunologists

ARTICLES

E-box activator of the C4 promoter is related to but distinct from the transcription factor upstream stimulating factor

MD Galibert, Y Miyagoe and T Meo
Unite d'Immunogenetique Institut National de la Sante et de la Recherche Medicale Institut Pasteur, Paris, France.

The murine C4 promoter contains a motif (E-C4) active in transcriptional activation whose structure complies with the E-box consensus sequence recognized by the helix-loop-helix transcription factors. This site is found also in human and rat C4 promoters and has the structure (-75) CACGTG (-70) characteristic of the class B subset of b-helix-loop-helix-zipper proteins. We have challenged the hypothesis that the protein factor responsible for the E-C4-mediated transcriptional activation is identical to one of the previously characterized nuclear factors. The molecular mass of the E-C4 factor is slightly bigger than that of Hela upstream stimulating factor (USF) (43/44 kDa). Moreover, the nucleotides immediately adjoining the E-C4 core sequence contribute to the distinctive fine specificity of the E- C4 factor. Optimized USF and MYC DNA-binding sites, which differ in the nucleotides bordering the hexanucleotide box displace the E-C4 factor in competition assays but with lesser efficiency than the E-C4 site itself. Finally, the E-C4 factor fails to exhibit the heat resistance characteristic of USF proteins. The results show that the E-C4 transcription factor has DNA binding properties overlapping those of other helix-loop-helix proteins but is structurally distinct from the factors so far described. Although C4 is not the first liver gene endowed with an E-box-mediated activation, it affords the first example where such activation takes place in the context of a TATA-less promoter, and is functionally linked to an initiator element-dependent transcription.

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