Single-molecule states link transcription factor binding to gene expression.

ABSTRACT: The binding of multiple transcription factors (TFs) to genomic enhancers drives gene expression in mammalian cells¹. However, the molecular details that link enhancer sequence to TF binding, promoter state and transcription levels remain unclear. Here we applied single-molecule footprinting^2,3 to measure the simultaneous occupancy of TFs, nucleosomes and other regulatory proteins on engineered enhancer-promoter constructs with variable numbers of TF binding sites for both a synthetic TF and an endogenous TF involved in the type I interferon response. Although TF binding events on nucleosome-free DNA are independent, activation domains recruit cofactors that destabilize nucleosomes, driving observed TF binding cooperativity. Average TF occupancy linearly determines pro

SUBMITTER: Doughty BR 

PROVIDER: S-EPMC12326879 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature