E-box activator of the C4 promoter is related to but distinct from the transcription factor upstream stimulating factor.
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.
Galibert
M D
MD
Unité d'Immunogénétique Institut National de la Santé et de la Recherche Médicale Institut Pasteur, Paris, France.
Miyagoe
Y
Y
Meo
T
T
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D003181:Complement C4 / Q000235:genetics*; D004247:DNA / Q000378:metabolism; D006358:Hot Temperature; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D015534:Trans-Activators / Q000378:metabolism*
D003181:Complement C4; D015534:Trans-Activators; D004247:DNA