The ubiquitously expressed cellular upstream stimulatory factor (USF) consists of 43 kDa (USF-1) and 44 kDa (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 upstream stimulatory factor that binds the core sequence CACGTG in the adenovirus late promoter. These findings, together with the demonstration of cooperative interaction between USF and the initiator-binding protein TFII-I, raise the possibility of a more general involvement of USF in transcriptional regulation. While expression of both USF-1 and USF-2 species is ubiquitous, different ratios of USF homo- and hetero-dimers are found in different cell types.