Evidence map›Paper›PMID 41308636›Full record

ArticleCell2026

Thermodynamic principles link in vitro transcription factor affinities to single-molecule chromatin states in cells.

Julia M Schaepe, Torbjörn Fries, Benjamin R Doughty, Vivekanandan Ramalingam, Betty B Liu, Olivia J Crocker, Georgi K Marinov, Michaela M Hinks, Emil Marklund, William J Greenleaf

Abstract read
In one paragraph

Article in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed.

  1. Exchange dynamics and kinetic control of gene regulation complexes.Nature reviews. Molecular cell biology · 2026
    Review
  2. Review
  3. Article
  4. Article
  5. Current Challenges of Transcription Compartmentalization Research.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  6. Article
  7. Article
  8. Chromatin association promotes UBR5-mediated degradation of Rb.bioRxiv : the preprint server for biology · 2026
    Article
  9. Article
  10. Article
  11. Article
  12. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Julia M SchaepeBioengineering Department, Stanford University, Stanford, CA 94305, USA.
Torbjörn FriesScience for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
Benjamin R DoughtyGenetics Department, Stanford University, Stanford, CA 94305, USA.
Vivekanandan RamalingamGenetics Department, Stanford University, Stanford, CA 94305, USA.
Betty B LiuBioengineering Department, Stanford University, Stanford, CA 94305, USA.
Olivia J CrockerGenetics Department, Stanford University, Stanford, CA 94305, USA.
Georgi K MarinovGenetics Department, Stanford University, Stanford, CA 94305, USA.
Michaela M HinksBioengineering Department, Stanford University, Stanford, CA 94305, USA.
Emil MarklundScience for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden. Electronic address: emil.marklund@scilifelab.se.
William J GreenleafGenetics Department, Stanford University, Stanford, CA 94305, USA; Department of Applied Physics, Stanford University, Stanford, CA 94205, USA. Electronic address: wjg@stanford.edu.

Funding

VACCINE INDUCED IMMUNITY IN THE YOUNG AND AGEDU19AI057266 · NIAID · EMORY UNIVERSITY · PI Rafi Ahmed · 2003 to 2026
$81.7M
Special EquipmentP50HG007735 · NHGRI · STANFORD UNIVERSITY · PI SNYDER, MICHAEL P. · 2014 to 2018
$15.2M
High-throughput systematic characterization of regulatory element functionUM1HG009436 · NHGRI · STANFORD UNIVERSITY · PI BASSIK, MICHAEL C, GREENLEAF, WILLIAM JAMES · 2017 to 2021
$5.4M
Combinatorial Cell State EngineeringDP1HG013599 · NHGRI · STANFORD UNIVERSITY · PI William James Greenleaf · 2023 to 2026
$5.4M
Genetics and Developmental Biology Training ProgramT32GM141828 · NIGMS · STANFORD UNIVERSITY · PI MARGARET T FULLER, Gavin J Sherlock · 2022 to 2026
$2.6M
Defining and perturbing gene regulatory dynamics in the developing human brainR01NS128028 · NINDS · STANFORD UNIVERSITY · PI William James Greenleaf · 2023 to 2026
$2.4M
Defining and perturbing gene regulatory dynamics in the developing human heart to understand mechanisms of congenital heart defectsR01HL171611 · NHLBI · STANFORD UNIVERSITY · PI William James Greenleaf · 2024 to 2026
$2.1M
Fast, powerful, scalable, usable, and distributable methods for multi-modal single cell analysesR01HG013317 · NHGRI · STANFORD UNIVERSITY · PI William James Greenleaf · 2024 to 2026
$2.1M
NHGRI NIH HHS DP1 HG013599NHGRI NIH HHS P50 HG007735NHGRI NIH HHS R01 HG013317NHGRI NIH HHS UM1 HG009436NHLBI NIH HHS R01 HL171611NIAID NIH HHS U19 AI057266NIGMS NIH HHS T32 GM141828NINDS NIH HHS R01 NS128028
6 · The paper itself

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 Krüppel-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.

Indexed as

ChromatinKruppel-Like Transcription FactorsTranscription FactorsBinding SitesDNAHumansKineticsNucleosomesNucleotide MotifsProtein BindingThermodynamicsChromatinDNAerythroid Kruppel-like factorKruppel-Like Transcription FactorsNucleosomesTranscription Factorsbiophysical modelschromatin accessibilitydeep learning modelseKLF/KLF1kineticssingle-molecule footprintingtarget searchthermodynamicstranscription factor binding

Identifiers

PMID41308636
PMCPMC13397507

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.