The regulatory element TGACGTCA is found upstream of a number of viral and cellular genes. This element has been demonstrated to mediate cyclic AMP induction of cellular genes and activation of viral genes. A group of closely related cellular genes known as cyclic AMP-response element binding proteins (CREB) or activating transcription factor (ATF) have been found to bind to this motif and mediate activation by cyclic AMP and the adenovirus E1A protein. One of these genes, CREB1, was previously mapped to human chromosome 2q32.3-q34. Southern blot analysis of genomic DNA from a panel of mouse-human somatic cell hybrids indicated that the CREB2 gene, another member of this family, also resides on human chromosome 2. In situ hybridization further regionalized this gene to 2q24.1-q32. Thus, the genes for CREB1 and CREB2 that have only limited DNA sequence homology map to a similar region of the long arm of chromosome 2, though whether they are part of a gene cluster is unclear.