THE SURF-1 AND SURF-2 GENES AND THEIR ESSENTIAL BIDIRECTIONAL PROMOTER ELEMENTS ARE CONSERVED BETWEEN MOUSE AND HUMAN

The organization of the Surfeit locus and the juxtaposition of at leas t five of the Surfeit genes (Surf-1 to -5) are conserved between mouse and human (Williams et al., 1988; Yon et al., 1993). In the mouse, th e heterogeneous transcription start sites of the divergent Surf-1 and Surf-2 genes are separated by a maximum of only 73 bp (Williams and Fr ied, 1986). This region contains a bidirectional promoter composed of three major factor binding sites required for the efficient expression of both the Surf-1 and Surf-2 genes (Lennard and Fried, 1991). Here w e report the isolation and characterization of the human Surf-1 and Su rf-2 genes and their intergenic region. Although the major Surf-1 and Surf-2 transcription start sites are separated by 97 bp in the human a nd there are multiple differences in the mouse and human sequence betw een and around the transcriptional start sites, there is high conserva tion of the sequence specifying the three major factor binding sites o f the bidirectional promoter. The three factor binding sites (HSu1, 2, and 3) present within the human promoter bind nuclear factors, of whi ch the binding of HSu1 and HSu2 are competed by oligonucleotides carry ing the corresponding mouse factor binding sites. The HSu3 site binds factors that are similar but apparently not direct homologs of those t hat bind to the equivalent mouse sequences. Human Surf-1 and Surf-2 cD NAs have been cloned and sequenced. The putative human Surf-1 and Surf -2 proteins are 77% and 69% identical to the corresponding mouse prote ins.