CHARACTERIZATION OF NERF, A NOVEL TRANSCRIPTION FACTOR-RELATED TO THEETS FACTOR ELF-1

We have cloned the gene for a novel Ets-related transcription factor, new Ets-related factor (NERF), from human spleen, fetal liver, and bra in. Comparison of the deduced amino acid sequence of NE;RF with those of other members of the Ets family reveals that the level of homology to ELF-1, which is involved in the regulation of several T- and B-cell -specific genes, is highest. Homologies are clustered in the putative DNA binding domain in the middle of the protein, a basic domain just u pstream of this domain, and several shorter stretches of homology towa rds the amino terminus. The presence of two predominant NERF transcrip ts in various fetal and adult human tissues is due to at least three a lternative splice products, NERF-1a, NERF-1b, and NERF-2, which differ in their amino termini and their expression in different tissues. Onl y NERF-2 and ELF-1, and not NERF-1a and NERF-1b, function as transcrip tional activators of the lyn and blk gene promoters, although all isof orms of NERF bind with affinities similar to those of ELF-1 to a varie ty of Ets binding sites in, among others, the blk, lck, lyn, mb-1, and immunoglobulin H genes and are expressed at similar levels. Since NER F and ELF-1 are coexpressed in B and T cells, both might be involved i n the regulation of the same genes.