Functional cooperativity between protein molecules bound at two distinct sequence elements of the immunoglobulin heavy-chain promoter.
Immunoglobulin heavy-chain gene promoters contain two conserved upstream sequence elements, octamer and heptamer, both of which are required for normal cell type-specific promoter function in vivo. The octamer sequence motif 5'-ATGCAAAT-3', and its precise inverse, are strongly conserved in heavy- and light-chain gene promoters and are important determinants for the lymphoid-specific function of these promoters and of the heavy-chain enhancer. The heptameric sequence element with the consensus 5'-CTCATGA-3' (refs 3 and 4) is also required in addition to the octamer for full lymphoid-specific activity of heavy-chain promoters. Although these two elements have no sequence similarity, they are both recognized in vitro by the ubiquitous octamer transcription factor OTF-1 (reviewed refs 13 and 14) and the lymphoid-specific OTF-2 (reviewed in refs 15 and 16). Here we show that purified OTF-2 binds cooperatively to the immunoglobulin heptamer and octamer elements so that interaction with the octamer element facilitates binding of OTF-2 to the heptamer motif. More important, cooperativity in OTF-2 binding is closely mirrored by functional cooperation between the heptamer and octamer elements in activating transcription from the heavy-chain promoter in vitro.
Poellinger
L
L
Laboratory of Biochemistry and Molecular Biology, Rockefeller University, New York 10021.
Yoza
B K
BK
Roeder
R G
RG
D001483:Base Sequence; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D002051:Burkitt Lymphoma / Q000235:genetics; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D014157:Transcription Factors