{"entity": "researcher", "timestamp": "2026-09-06T14:52:34.972Z", "family": "Bintu", "given": "Lacramioara", "initials": "L", "orcid": "0000-0001-5443-6633", "affiliations": ["Bioengineering Department, Stanford University, Stanford, CA, USA. lbintu@stanford.edu."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/34583bd9dd894dd1bbf0f91e548f0643.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/34583bd9dd894dd1bbf0f91e548f0643"}}, "publications": [{"entity": "publication", "iuid": "e29b74ef4d1c4064a9651c3b1d4680c3", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e29b74ef4d1c4064a9651c3b1d4680c3.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e29b74ef4d1c4064a9651c3b1d4680c3"}}, "title": "Single-molecule states link transcription factor binding to gene expression.", "authors": [{"family": "Doughty", "given": "Benjamin R", "initials": "BR", "orcid": "0000-0003-0447-4468", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4275613fa5cd43aca79c95189a33cd7d.json"}}, {"family": "Hinks", "given": "Michaela M", "initials": "MM"}, {"family": "Schaepe", "given": "Julia M", "initials": "JM", "orcid": "0000-0003-0416-0469", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d029b6f8e7f346e098d7bef07a7d21a3.json"}}, {"family": "Marinov", "given": "Georgi K", "initials": "GK", "orcid": "0000-0003-1822-7273", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f1f4bf8bc7704c6d9be2ee6026666346.json"}}, {"family": "Thurm", "given": "Abby R", "initials": "AR", "orcid": "0000-0002-1819-3192", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9f2defd0b81f4642933396051586ae04.json"}}, {"family": "Rios-Martinez", "given": "Carolina", "initials": "C"}, {"family": "Parks", "given": "Benjamin E", "initials": "BE", "orcid": "0000-0002-0261-7472", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bd6e49bdfbd14cf68fdf1b7c6d5ef3fe.json"}}, {"family": "Tan", "given": "Yingxuan", "initials": "Y"}, {"family": "Marklund", "given": "Emil", "initials": "E", "orcid": "0000-0002-1150-7304", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a5e6f08a55df4af5927d91bf5f3f0870.json"}}, {"family": "Dubocanin", "given": "Danilo", "initials": "D"}, {"family": "Bintu", "given": "Lacramioara", "initials": "L", "orcid": "0000-0001-5443-6633", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/34583bd9dd894dd1bbf0f91e548f0643.json"}}, {"family": "Greenleaf", "given": "William J", "initials": "WJ", "orcid": "0000-0003-1409-3095", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ec47da61f6024af7b53412aadb7e6c8a.json"}}], "type": "journal article", "published": "2024-11-20", "journal": {"title": "Nature", "issn": "1476-4687", "issn-l": "0028-0836"}, "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 footprinting2,3 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 promoter activity, and we decompose TF strength into separable binding and activation terms. Finally, we develop thermodynamic and kinetic models that quantitatively predict both the enhancer binding microstates and gene expression dynamics. This work provides a template for the quantitative dissection of distinct contributors to gene expression, including TF activation domains, concentration, binding affinity, binding site configuration and recruitment of chromatin regulators.", "doi": "10.1038/s41586-024-08219-w", "pmid": "39567683", "labels": {"Emil Marklund": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pii", "key": "10.1038/s41586-024-08219-w"}], "notes": [], "created": "2024-11-21T15:38:21.124Z", "modified": "2024-11-21T15:40:14.330Z"}, {"entity": "publication", "iuid": "7d34cdb33c8c4af9a00320d21cefff95", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/7d34cdb33c8c4af9a00320d21cefff95.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/7d34cdb33c8c4af9a00320d21cefff95"}}, "title": "Single-molecule chromatin configurations link transcription factor binding to expression in human cells.", "authors": [{"family": "Doughty", "given": "Benjamin R", "initials": "BR", "orcid": "0000-0003-0447-4468", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4275613fa5cd43aca79c95189a33cd7d.json"}}, {"family": "Hinks", "given": "Michaela M", "initials": "MM"}, {"family": "Schaepe", "given": "Julia M", "initials": "JM", "orcid": "0000-0003-0416-0469", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d029b6f8e7f346e098d7bef07a7d21a3.json"}}, {"family": "Marinov", "given": "Georgi K", "initials": "GK", "orcid": "0000-0003-1822-7273", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f1f4bf8bc7704c6d9be2ee6026666346.json"}}, {"family": "Thurm", "given": "Abby R", "initials": "AR", "orcid": "0000-0002-1819-3192", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9f2defd0b81f4642933396051586ae04.json"}}, {"family": "Rios-Martinez", "given": "Carolina", "initials": "C", "orcid": "0000-0001-6927-2256", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7d0e38d028ef400595cab26592098c59.json"}}, {"family": "Parks", "given": "Benjamin E", "initials": "BE", "orcid": "0000-0002-0261-7472", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bd6e49bdfbd14cf68fdf1b7c6d5ef3fe.json"}}, {"family": "Tan", "given": "Yingxuan", "initials": "Y", "orcid": "0000-0001-6674-3219", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2b9a75f58a364bbd9c00322090300d8d.json"}}, {"family": "Marklund", "given": "Emil", "initials": "E", "orcid": "0000-0002-1150-7304", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a5e6f08a55df4af5927d91bf5f3f0870.json"}}, {"family": "Dubocanin", "given": "Danilo", "initials": "D", "orcid": "0000-0003-0330-5814", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0d76367d02e24b01ae27f92d9d3dac9d.json"}}, {"family": "Bintu", "given": "Lacramioara", "initials": "L", "orcid": "0000-0001-5443-6633", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/34583bd9dd894dd1bbf0f91e548f0643.json"}}, {"family": "Greenleaf", "given": "William J", "initials": "WJ", "orcid": "0000-0003-1409-3095", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ec47da61f6024af7b53412aadb7e6c8a.json"}}], "type": "preprint", "published": "2024-02-04", "journal": {"title": "bioRxiv", "issn": "2692-8205", "issn-l": null}, "abstract": "The binding of multiple transcription factors (TFs) to genomic enhancers activates gene expression in mammalian cells. However, the molecular details that link enhancer sequence to TF binding, promoter state, and gene expression levels remain opaque. We applied single-molecule footprinting (SMF) to measure the simultaneous occupancy of TFs, nucleosomes, and components of the transcription machinery on engineered enhancer/promoter constructs with variable numbers of TF binding sites for both a synthetic and an endogenous TF. We find that activation domains enhance a TF's capacity to compete with nucleosomes for binding to DNA in a BAF-dependent manner, TF binding on nucleosome-free DNA is consistent with independent binding between TFs, and average TF occupancy linearly contributes to promoter activation rates. We also decompose TF strength into separable binding and activation terms, which can be tuned and perturbed independently. Finally, we develop thermodynamic and kinetic models that quantitatively predict both the binding microstates observed at the enhancer and subsequent time-dependent gene expression. This work provides a template for quantitative dissection of distinct contributors to gene activation, including the activity of chromatin remodelers, TF activation domains, chromatin acetylation, TF concentration, TF binding affinity, and TF binding site configuration.", "doi": "10.1101/2024.02.02.578660", "pmid": "38352517", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10862896"}, {"db": "pii", "key": "2024.02.02.578660"}], "notes": [], "created": "2026-08-20T10:52:01.926Z", "modified": "2026-08-20T10:52:02.194Z"}]}