{"entity": "researcher", "timestamp": "2026-07-20T01:23:38.344Z", "family": "Schaepe", "given": "Julia M", "initials": "JM", "orcid": "0000-0003-0416-0469", "affiliations": ["Department of Bioengineering, Stanford University, Stanford, CA 94305, USA."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/d029b6f8e7f346e098d7bef07a7d21a3.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/d029b6f8e7f346e098d7bef07a7d21a3"}}, "publications": [{"entity": "publication", "iuid": "172ce1eabdaa4a6ba669e9457d669dc4", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/172ce1eabdaa4a6ba669e9457d669dc4.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/172ce1eabdaa4a6ba669e9457d669dc4"}}, "title": "Thermodynamic principles link in vitro transcription factor affinities to single-molecule chromatin states in cells", "authors": [{"family": "Schaepe", "given": "Julia M", "initials": "JM", "orcid": "0000-0003-0416-0469", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d029b6f8e7f346e098d7bef07a7d21a3.json"}}, {"family": "Fries", "given": "Torbj\u00f6rn", "initials": "T"}, {"family": "Doughty", "given": "Benjamin R", "initials": "BR", "orcid": "0000-0003-0447-4468", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4275613fa5cd43aca79c95189a33cd7d.json"}}, {"family": "Ramalingam", "given": "Vivekanandan", "initials": "V"}, {"family": "Liu", "given": "Betty B", "initials": "BB"}, {"family": "Crocker", "given": "Olivia J", "initials": "OJ"}, {"family": "Marinov", "given": "Georgi K", "initials": "GK", "orcid": "0000-0003-1822-7273", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f1f4bf8bc7704c6d9be2ee6026666346.json"}}, {"family": "Hinks", "given": "Michaela M", "initials": "MM"}, {"family": "Marklund", "given": "Emil", "initials": "E"}, {"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": "2026-01-00", "journal": {"title": "Cell", "issn": "0092-8674", "volume": "189", "issue": "1", "pages": "307-322.e23", "issn-l": null}, "abstract": "The molecular details governing transcription factor (TF) binding and the formation of accessible chromatin are not yet quantitatively understood-including how sequence context modulates affinity, how TFs search DNA, the kinetics of TF occupancy, and how motif grammars coordinate binding. To resolve these questions for a human TF, erythroid Kr\u00fcppel-like factor (eKLF/KLF1), we quantitatively compare, in high throughput, in vitro TF binding rates and affinities with in vivo single-molecule TF and nucleosome occupancies and in vivo-derived deep learning models. We find that 40-fold flanking sequence effects on affinity are consistent with distal flanks tuning TF search parameters and captured by a linear energy model. Motif recognition probability, rather than time in the bound state, drives affinity changes, and in vitro and in nuclei measurements exhibit consistent, minutes-long TF residence times. Finally, in vitro biophysical parameters predict in vivo sequence preferences and single-molecule chromatin states for unseen motif grammars.", "doi": "10.1016/j.cell.2025.11.008", "pmid": "41308636", "labels": {"Emil Marklund": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pii", "key": "S0092-8674(25)01300-5"}], "notes": [], "created": "2025-11-27T16:53:03.536Z", "modified": "2026-06-03T09:43:36.683Z"}, {"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": "2b4d8d7f29264a19ab3c1e975d0ccccc", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/2b4d8d7f29264a19ab3c1e975d0ccccc.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/2b4d8d7f29264a19ab3c1e975d0ccccc"}}, "title": "Short tandem repeats bind transcription factors to tune eukaryotic gene expression.", "authors": [{"family": "Horton", "given": "Connor A", "initials": "CA", "orcid": "0000-0001-6018-3556", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e9e41811947f4df29d8a716921f05b79.json"}}, {"family": "Alexandari", "given": "Amr M", "initials": "AM", "orcid": "0000-0001-8655-8109", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/488824b08e4f4f2da463c3f2a2008908.json"}}, {"family": "Hayes", "given": "Michael G B", "initials": "MGB", "orcid": "0000-0001-5315-7042", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1841ebc579fe47b9848cfadad63d2285.json"}}, {"family": "Marklund", "given": "Emil", "initials": "E", "orcid": "0000-0002-1150-7304", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a5e6f08a55df4af5927d91bf5f3f0870.json"}}, {"family": "Schaepe", "given": "Julia M", "initials": "JM", "orcid": "0000-0003-0416-0469", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d029b6f8e7f346e098d7bef07a7d21a3.json"}}, {"family": "Aditham", "given": "Arjun K", "initials": "AK", "orcid": "0000-0002-9839-7733", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0c6940ecc31b4b079149a81f67663cef.json"}}, {"family": "Shah", "given": "Nilay", "initials": "N", "orcid": "0000-0002-0081-8537", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f12aeecea3c84d7bbaecb9e02cf4c081.json"}}, {"family": "Suzuki", "given": "Peter H", "initials": "PH", "orcid": "0000-0002-6108-0273", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e88d872d5a7440faa6f58640589c1e55.json"}}, {"family": "Shrikumar", "given": "Avanti", "initials": "A", "orcid": "0000-0002-6443-4671", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fd5e4d1511b8470c834795ab2dcc4b09.json"}}, {"family": "Afek", "given": "Ariel", "initials": "A", "orcid": "0000-0001-8584-9879", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a1ae9fd5abd44f5b9f48776515b80b1e.json"}}, {"family": "Greenleaf", "given": "William J", "initials": "WJ", "orcid": "0000-0003-1409-3095", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ec47da61f6024af7b53412aadb7e6c8a.json"}}, {"family": "Gord\u00e2n", "given": "Raluca", "initials": "R"}, {"family": "Zeitlinger", "given": "Julia", "initials": "J", "orcid": "0000-0002-5172-3335", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1c220136969b4fe2b694135c91a2ce49.json"}}, {"family": "Kundaje", "given": "Anshul", "initials": "A", "orcid": "0000-0003-3084-2287", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ed56d6465b0d497fa62ea77608c66e2b.json"}}, {"family": "Fordyce", "given": "Polly M", "initials": "PM", "orcid": "0000-0002-9505-0638", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b31df914dcaa45f7b2d30b9c30536d82.json"}}], "type": "journal article", "published": "2023-09-22", "journal": {"title": "Science (New York, N.Y.)", "issn": "1095-9203", "volume": "381", "issue": "6664", "pages": "eadd1250", "issn-l": "0036-8075"}, "abstract": "Short tandem repeats (STRs) are enriched in eukaryotic cis-regulatory elements and alter gene expression, yet how they regulate transcription remains unknown. We found that STRs modulate transcription factor (TF)-DNA affinities and apparent on-rates by about 70-fold by directly binding TF DNA-binding domains, with energetic impacts exceeding many consensus motif mutations. STRs maximize the number of weakly preferred microstates near target sites, thereby increasing TF density, with impacts well predicted by statistical mechanics. Confirming that STRs also affect TF binding in cells, neural networks trained only on in vivo occupancies predicted effects identical to those observed in vitro. Approximately 90% of TFs preferentially bound STRs that need not resemble known motifs, providing a cis-regulatory mechanism to target TFs to genomic sites.", "doi": "10.1126/science.add1250", "pmid": "37733848", "labels": {"Emil Marklund": null, "SciLifeLab Fellow": null}, "xrefs": [], "notes": [], "created": "2024-11-21T15:37:40.058Z", "modified": "2024-11-21T15:40:12.193Z"}]}