We describe here a novel member of the bZIP family of DNA-binding proteins, designated E4BP4, that displays an unusual DNA-binding specificity which overlaps that of the activating transcription factor family of factors. Transcription initiation depends to a large extent upon the activating capacity of specific protein factors which bind to gene regulatory regions, usually upstream of the transcription start site (33,38,43). However, regulation of transcription also involves inhibitory processes, and a growing number of DNA-binding factors which repress transcription in a gene-specific manner have recently been described elsewhere (3,5,11,24,26,34,50). Various mechanisms as to how transcriptional inhibition is effected may be envisaged. One such mechanism is steric hindrance of or direct competition for DNA binding with positively acting transcription factors. An example of this type of transcriptional repression is the ability of the transcription factor AP1 to inhibit basal and retinoic acid-induced expression of the osteocalcin gene by competition for binding to a common sequence element which is also recognized by the retinoic acid receptor (49). Repression of another kind again involves inhibition of DNA binding of a transcriptional activator, but in this case through protein-protein interactions. Examples of this type of repression include the mutual inhibition of DNA binding of AP1 proteins and the glucocorticoid receptor (48, 55) and negative regulation by the formation of non-DNA-binding heterodimers between helix-loop-helix proteins and the Id protein (5). A third type of transcriptional repressor does not suppress transcription through inhibition of the DNA binding of transcriptional activators. Repressors of this type are DNA-binding proteins whose action appears to be a direct down regulation of transcription. Such repressors will here be collectively termed active transcriptional repressors. Examples include the Drosophila kruppel (34) and engrailed proteins (17, 24), the human kruppel-related factor YY1 (50), and the Wilms' tumor gene product (36).Transcription factors are conveniently divided into a number of structurally related families. The bZIP factors constitute one such family and share an amphipathic a-helical dimerization domain characterized by a heptad repeat of leucine residues, the leucine zipper (30

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We describe here a novel member of the bZIP family of DNA-binding proteins, designated E4BP4, that displays an unusual DNA-binding specificity which overlaps that of the activating transcription factor family of factors. When expressed in a transient transfection assay with a suitable reporter plasmid, E4BP4 strongly repressed transcription in a DNA-binding-site-dependent manner. Examination of a series of deletion mutants revealed that sequences responsible for the repressing potential of E4BP4 lie within the carboxyl-terminal region of the protein. No similarity was found between this region and the repressing domains of other known eukaryotic transcriptional repressors.