Synergistic activation of transcription by multiple binding sites for NF-kappa B even in absence of co-operative factor binding to DNA.
Regulation of eukaryotic genes is largely governed by multiple cis-acting DNA sequences recognized by specific transcription factors. The transcription factor NF-kappa B has been implicated as an important regulator of cellular and viral genes, including those of immunoglobulin kappa light chain, interleukin-2, beta-interferon, HIV-1 and cytomegalovirus. We have analyzed the effect of increasing the number of NF-kappa B sites, located directly upstream from the TATA box. Four copies of the sequence gave a more than 100-fold stimulation relative to a single copy, suggesting that NF-kappa B proteins act synergistically to bring about this dramatic increase in transcription. By DNase I footprinting we demonstrated factor binding to two adjacent NF-kappa B sites in vitro. However, we found no evidence for co-operative binding to these DNA sites. We propose that the high transcriptional activity results from another type of co-operation, based on multiple weak interactions of the NF-kappa B factors with another component of the transcription apparatus, perhaps RNA polymerase II itself.
Institut für Molekularbiologie II, Universität Zürich, Switzerland.
M
M
Pettersson
W
W
Schaffner
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D016328:NF-kappa B; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D016328:NF-kappa B; D014157:Transcription Factors; D004247:DNA