Cross-family dimerization of transcription factors Fos/Jun and ATF/CREB alters DNA binding specificity.

TLDR

Fos/Jun and ATF/CREB transcription factors couple extracellular signals to gene expression changes by forming leucine‑zipper mediated dimers that bind DNA. The study proposes grouping Fos/Jun and ATF/CREB into a single transcription factor superfamily. Cross‑family heterodimers between Fos/Jun and ATF/CREB form and exhibit unique DNA binding specificities distinct from their homodimers, showing the two families are not as distinct as previously thought.

Abstract

The Fos/Jun and ATF/CREB families of transcription factors function in coupling extracellular signals to alterations in expression of specific target genes. Like many eukaryotic transcription factors, these proteins bind to DNA as dimers. Dimerization is mediated by a structure known as the "leucine-zipper" motif. Although Fos/Jun and ATF/CREB were previously thought to interact preferentially with different DNA regulatory elements (the AP-1/TRE and ATF/CRE sites, respectively), we find that members of these two families form selective cross-family heterodimers. The resulting heterodimers display distinguishable DNA binding specificities from each other and from their parental homodimers. These findings indicate that the Fos/Jun and ATF/CREB families of transcription factors are not as distinct as was previously thought. We suggest that they can be grouped into a superfamily of transcription factors.