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 al so contains putative sites-for Ets proteins. One of the Ets sites, whi ch we refer to as EBS4, is located next to an NF-kappa B/Rel binding s ite, kB3, which is absolutely required for activity of the promoter in Jurkat T cells in response to activation by phorbol 12-myristate 13-a cetate (PMA), PMA/ionomycin, or the Tax protein from human T cell leuk emia 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 i s bound by Ets-1, Elf-1, and other species. Overexpression of Ets-l au gments the response to PMA/ionomycin and this is reduced by mutation o f EBS4. Elf-1 has less effect in conjunction with PMA/ionomycin, but b y itself activates the promoter 12-fold. This activation is only partl y 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 efficie ntly as the wild-type. Ets proteins may be responsible for fine-tuning the activity of the nfkb1 gene in a cell-type-specific manner.