ISOLATION OF NF-E2-RELATED FACTOR-2 (NRF2), A NF-E2-LIKE BASIC LEUCINE-ZIPPER TRANSCRIPTIONAL ACTIVATOR THAT BINDS TO THE TANDEM NF-E2 AP1 REPEAT OF THE BETA-GLOBIN LOCUS-CONTROL REGION/

Hypersensitive site 2 located in the beta-globin locus control region confers high levels of expression to the genes of the beta-globin clus ter. A tandem repeat of the consensus sequence for the transcription f actors AP1 and NF-E2 (activating protein 1 and nuclear factor erythroi d 2, respectively) is present within hypersensitive site 2 and is abso lutely required for strong enhancer activity. This sequence binds, in vitro and in vivo, to ubiquitous proteins of the AP1 family and to the recently cloned erythroid-specific transcription factor NF-E2. Using the tandem repeat as a recognition site probe to screen a lambda gt11 cDNA expression library from K562 cells, we isolated several DNA bindi ng proteins. Here, we report the characterization of one of the clones isolated. The gene, which we named Nrf2 (NF-E2-related factor 2), is encoded within a 2.2-kb transcript and predicts a 66-kDa protein with a basic leucine zipper DNA binding domain highly homologous to that of NF-E2. Although Nrf2 is expressed ubiquitously, a role of this protei n in mediating enhancer activity of hypersensitive site 2 in erythroid cells cannot be excluded. In this respect, Nrf2 contains a powerful a cidic activation domain that may participate in the transcriptional st imulation of beta-globin genes.