The study by Hai and Curran investigates the cross-family dimerization of transcription factors Fos/Jun and ATF/CREB, which are known to function in coupling extracellular signals to changes in gene expression. These proteins bind to DNA as dimers, mediated by a "leucine-zipper" motif. Initially, it was thought that Fos/Jun and ATF/CREB interact preferentially with different DNA regulatory elements (AP-1/TRE and ATF/CRE sites, respectively). However, the authors found that members of these two families can form selective heterodimers, which display distinct DNA binding specificities compared to their parental homodimers. This suggests that the Fos/Jun and ATF/CREB families are not as distinct as previously thought and can be grouped into a superfamily of transcription factors. The study used in vitro-transcribed mRNA and coimmunoprecipitation and gel-shift assays to demonstrate the formation of these heterodimers and their altered DNA binding activities. The findings indicate that the cross-family dimerization plays a role in signal transduction processes within the nucleus, potentially mediating diverse physiological responses to environmental stimuli.The study by Hai and Curran investigates the cross-family dimerization of transcription factors Fos/Jun and ATF/CREB, which are known to function in coupling extracellular signals to changes in gene expression. These proteins bind to DNA as dimers, mediated by a "leucine-zipper" motif. Initially, it was thought that Fos/Jun and ATF/CREB interact preferentially with different DNA regulatory elements (AP-1/TRE and ATF/CRE sites, respectively). However, the authors found that members of these two families can form selective heterodimers, which display distinct DNA binding specificities compared to their parental homodimers. This suggests that the Fos/Jun and ATF/CREB families are not as distinct as previously thought and can be grouped into a superfamily of transcription factors. The study used in vitro-transcribed mRNA and coimmunoprecipitation and gel-shift assays to demonstrate the formation of these heterodimers and their altered DNA binding activities. The findings indicate that the cross-family dimerization plays a role in signal transduction processes within the nucleus, potentially mediating diverse physiological responses to environmental stimuli.