The nfkb1 promoter is controlled by proteins of the Ets family.
The gene encoding NFKB1 is autoregulated, responding to NF-kappa B/Rel activation through NF-kappa B binding sites in its promoter, which also contains putative sites for Ets proteins. One of the Ets sites, which we refer to as EBS4, is located next to an NF-kappa B/Rel binding site, kB3, which is absolutely required for activity of the promoter in Jurkat T cells in response to activation by phorbol 12-myristate 13-acetate (PMA), PMA/ionomycin, or the Tax protein from human T cell leukemia virus type I. We show that EBS4 is, required for the full response of the nfkb1 promoter to PMA or PMA/ionomycin in Jurkat cells. EBS4 is bound by Ets-1, Elf-1, and other species. Overexpression of Ets-1 augments the response to PMA/ionomycin and this is reduced by mutation of EBS4. Elf-1 has less effect in conjunction with PMA/ionomycin, but by itself activates the promoter 12-fold. This activation is only partly affected by mutation of EBS4, and a mutant promoter that binds Ets-1, but not Elf-1, at the EBS4 site responds to PMA/ionomycin as efficiently as the wild-type. Ets proteins may be responsible for fine-tuning the activity of the nfkb1 gene in a cell-type-specific manner.
Lambert
P F
PF
Macfarlane Burnet Centre for Medical Research, Fairfield, Victoria, Australia.
Ludford-Menting
M J
MJ
Deacon
N J
NJ
Kola
I
I
Doherty
R R
RR
D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D004268:DNA-Binding Proteins / Q000378:metabolism*; D036383:Ephrin-A2; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D019169:Jurkat Cells; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D052002:NF-kappa B p50 Subunit; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000235:genetics*; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; C494041:ETS1 protein, human; D036383:Ephrin-A2; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D011498:Protein Precursors; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate