The ubiquitously expressed cellular upstream stimulatory factor (USF) consists of USF-1 and USF-2 polypeptides which independently exhibit site-specific DNA binding and are members of the c-Myc-related family of regulatory factors containing helix-loop-helix domains. USF also contains a leucine repeat that is required for efficient DNA binding. USF was originally identified as an up- stream stimulatory factor that binds the core sequence CACGTG in the adeno- virus late promoter. These findings, together with the demonstration of coop- erative interaction between USF and the initiator-binding protein, TFII-I, raises the possibility of a more general involvement of USF in transcriptional regula- tion. While expression of both USF-1 and USF-2 species is ubiquitous, different ratios of USF homo- and heterodimers are found in different cell types.