{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Doughty BR"],"funding":["NHLBI NIH HHS","NHGRI NIH HHS","NINDS NIH HHS","NIGMS NIH HHS"],"pagination":["745-754"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12326879"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["636(8043)"],"pubmed_abstract":["The binding of multiple transcription factors (TFs) to genomic enhancers drives gene expression in mammalian cells<sup>1</sup>. However, the molecular details that link enhancer sequence to TF binding, promoter state and transcription levels remain unclear. Here we applied single-molecule footprinting<sup>2,3</sup> 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"],"journal":["Nature"],"pubmed_title":["Single-molecule states link transcription factor binding to gene expression."],"pmcid":["PMC12326879"],"funding_grant_id":["T32 GM145402","R01 HL171611","R35 GM128947","P50 HG007735","R01 HG013317","DP1 HG013599","UM1 HG009436","R01 NS128028"],"pubmed_authors":["Parks BE","Marklund E","Greenleaf WJ","Tan Y","Dubocanin D","Bintu L","Marinov GK","Doughty BR","Hinks MM","Schaepe JM","Rios-Martinez C","Thurm AR"],"additional_accession":[]},"is_claimable":false,"name":"Single-molecule states link transcription factor binding to gene expression.","description":"The binding of multiple transcription factors (TFs) to genomic enhancers drives gene expression in mammalian cells<sup>1</sup>. However, the molecular details that link enhancer sequence to TF binding, promoter state and transcription levels remain unclear. Here we applied single-molecule footprinting<sup>2,3</sup> 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","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Dec","modification":"2026-06-06T07:19:13.727Z","creation":"2026-06-06T03:06:53.885Z"},"accession":"S-EPMC12326879","cross_references":{"pubmed":["39567683"],"doi":["10.1038/s41586-024-08219-w"]}}