Evidence map›Paper›PMID 32910904›Full record

ArticleCell systems2020

A High-Throughput Genome-Integrated Assay Reveals Spatial Dependencies Governing Tcf7l2 Binding.

Tomasz Szczesnik, Lendy Chu, Joshua W K Ho, Richard I Sherwood

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell systems, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.2field-weighted citation impact, top 49% of its field
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

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  2. Using CRISPR to understand and manipulate gene regulation.Development (Cambridge, England) · 2021
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 5 countries.

Tomasz SzczesnikVictor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, University of New South Wales, Darlinghurst, NSW 2010, Australia; Department of Biosystems Science and Engineering, ETH Zürich, Mattenstrasse 26, Basel 4058, Switzerland.
Lendy ChuDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Joshua W K HoVictor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, University of New South Wales, Darlinghurst, NSW 2010, Australia; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Richard I SherwoodDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Hubrecht Institute, 3584 CT Utrecht, the Netherlands. Electronic address: rsherwood@rics.bwh.harvard.edu.
Harvard University · USSt Vincent's Clinic · AU

Funding

High-Throughput Native Context Mapping and Modeling of Regulatory DNAR01HG008754 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GIFFORD, DAVID K · 2016 to 2019
$2.7M
High-throughput methods for elucidating the control of chromatin accessibilityR01HG008363 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GIFFORD, DAVID K · 2015 to 2017
$2.3M
Predictive transcription factor modeling to program endodermal cell fatesK01DK101684 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI SHERWOOD, RICHARD I · 2014 to 2018
$670k
Systematic unlocking of airway stem cell differentiation programR21OD025309 · OD · BRIGHAM AND WOMEN'S HOSPITAL · PI SHERWOOD, RICHARD I · 2019 to 2020
$462k
NHGRI NIH HHS R01 HG008363NHGRI NIH HHS R01 HG008754NIDDK NIH HHS K01 DK101684NIH HHS R21 OD025309
6 · The paper itself

Abstract

Predicting where transcription factors bind in the genome from their in vitro DNA-binding affinity is confounded by the large number of possible interactions with nearby transcription factors. To characterize the in vivo binding logic for the Wnt effector Tcf7l2, we developed a high-throughput screening platform in which thousands of synthesized DNA phrases are inserted into a specific genomic locus, followed by measurement of Tcf7l2 binding by DamID. Using this platform at two genomic loci in mouse embryonic stem cells, we show that while the binding of Tcf7l2 closely follows the in vitro motif-binding strength and is influenced by local chromatin accessibility, it is also strongly affected by the surrounding 99 bp of sequence. Through controlled sequence perturbation, we show that Oct4 and Klf4 motifs promote Tcf7l2 binding, particularly in the adjacent ∼50 bp and oscillating with a 10.8-bp phasing relative to these cofactor motifs, which matches the turn of a DNA helix.

Indexed as

Binding SitesHigh-Throughput Screening AssaysHumansKruppel-Like Factor 4Transcription Factor 7-Like 2 ProteinTranscription FactorsKLF4 protein, humanKlf4 protein, mouseKruppel-Like Factor 4TCF7L2 protein, humanTranscription Factor 7-Like 2 ProteinTranscription FactorsCRISPR-Cas9DamIDGaussian processTcf7l2transcription factor

Identifiers

PMID32910904
PMCPMC7530048
OpenAlexW3084406332

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.