Internal regulatory interactions determine DNA binding specificity by a Hox transcription factor.

摘要: Abstract In developing bilaterans, the Hox transcription factor family regulates batteries of downstream genes to diversify serially repeated units. Given homeodomains bind a wider array DNA binding sites in vitro than are regulated by full-length protein vivo , regions outside homeodomain must aid site selection. Indeed, we find affinity for disparate sequences varies less 3-fold isolated from Drosophila Ultrabithorax Ia (UbxHD), whereas (UbxIa) differs more 10-fold. The rank order preferred also differs, further demonstrating distinct preferences. increased specificity UbxIa can be partially attributed I1 region, which lies adjacent and directly impacts energetics. Each three segments within I1—the Extradenticle-binding YPWM motif, six amino acids immediately N-terminal this eight abutting C-terminus—uniquely contribute specificity. Combination these synergistically modifies enhance Intriguingly, presence motif inhibits only Ubx–Extradenticle heterodimer sites, potentially functioning prevent Ubx monomers misregulating target genes. However, removal surrounding region allows inhibit Hox-only recognition sequences. Despite modular domain design proteins, results suggest that multiple form network regulatory interactions coordinate context- gene-specific responses. Since most nonhomeodomain not conserved between members, have potential highly homologous homeodomains.