A trans-acting peptide activates the yeast a1 repressor by raising its DNA-binding affinity

The cooperative binding of gene regulatory proteins to DNA is a common feat ure of transcriptional control in both prokaryotes and eukaryotes, It is ge nerally viewed as a simple energy coupling, through protein-protein interac tions, of two or more DNA-binding proteins, In this paper, we show that the simple view does not account for the cooperative DNA binding of al and alp ha 2, two homeodomain proteins from budding yeast, Rather, we show through the use of chimeric proteins and synthetic peptides that, upon heterodimeri zation, alpha 2 instructs at to bind DNA, This change is induced by contact with a peptide contributed by alpha 2, and this contact converts al from a weak to a strong DNA-binding protein. This explains, in part, how high DNA -binding specificity is achieved only when the two gene regulatory proteins conjoin, We also provide evidence that features of the a1-alpha 2 interact ion can serve as a model for other examples of protein-protein interactions , including that between the herpes virus transcriptional activator VP16 an d the mammalian homeodomain-containing protein Oct-1.