"Structure"-function relationships in eukaryotic transcription factors: The role of intrinsically disordered regions in gene regulation

Many principles of bacterial gene regulation have been foundational to understanding mechanisms of eu-karyotic transcription. However, stark structural and functional differences exist between eukaryotic and bacterial transcription factors that complicate inferring properties of the eukaryotic system from that of bac-teria. Here, we review those differences, focusing on the impact of intrinsically disordered regions on the ther-modynamic and kinetic parameters governing eukaryotic transcription factor interactions???both with other proteins and with chromatin. The prevalence of unstructured domains in eukaryotic transcription factors as well as their known impact on function call for more sophisticated knowledge of what mechanisms they support. Using the evidence available to date, we posit that intrinsically disordered regions are necessary for the complex and integrative functions of eukaryotic transcription factors and that only by understanding their rich biochemistry can we develop a deep molecular understanding of their regulatory mechanisms.