【Tokushima University】Mechanism of "Molecular Switch" Controlling Transcription Factor Hub Formation via Phase Separation Uncovered ~Structural Fluctuations Control Molecular Assembly of Transcription Factors~

A research group from Tokushima University and Hokkaido University has elucidated the detailed molecular mechanism by which Heat Shock Transcription Factor 1 (Hsf1), which protects cells from stress, is activated upon binding to DNA. Normally, Hsf1 exists in a self-inhibited state, but when DNA binds, the structural flexibility of its DNA-binding domain increases. This change releases a previously bound intrinsically disordered region (IDR), promoting interactions between IDRs and triggering biomolecular phase separation. This process efficiently gathers transcription factors to activate cell-protective genes. This study reveals at an atomic level how a local DNA binding event is converted into a widespread phenomenon like phase separation, and is expected to lead to new drug discovery concepts targeting the structural equilibrium of transcription factors.