Zinc finger–zinc finger interaction between the transcription factors, GATA-1 and Sp1

In contrast to the extensive understanding of the zinc finger–DNA interactions, less is known about zinc finger–zinc finger interactions. GATA-1 and Sp1 are transcription factors with zinc finger domains for DNA binding. The interaction between the GATA-1 and Sp1 zinc finger domains is important for synergistic transcriptional effects in erythroid genes. Despite the biological importance of the GATA-1 and Sp1 interaction, the molecular mechanism of the interaction remains unclear. We constructed a series of deletion mutants of the zinc finger domains of GATA-1 and Sp1 to identify the regions within the GATA-1 and Sp1 zinc finger domains that interact. The zinc finger–zinc finger interaction modes were also estimated from calorimetric measurements. This revealed that the interaction between the Sp1 and GATA-1 zinc finger domains was primarily electrostatic, and that the linker region of the Sp1 zinc fingers is important for the association with the GATA-1 zinc finger domains. We propose a new molecular mechanism for zinc finger–zinc finger interactions that should contribute to our understanding of the bio-functional role of the interaction between GATA-1 and Sp1.

Research highlights
► The zinc fingers of the transcription factors, Sp1 and GATA-1, interact with each other.
► The zinc finger–zinc finger interaction is an entropically driven process.
► The basic loop region of the GATA-1 zinc finger is involved in the interaction.
► The linker regions of the Sp1 zinc finger are involved in the interaction.
► A new function of the linker as a mediator of the protein–protein interaction is proposed.