Evidence map›Paper›PMID 39019045›Full record

ArticleMolecular cell2024

Systematic dissection of sequence features affecting binding specificity of a pioneer factor reveals binding synergy between FOXA1 and AP-1.

Cheng Xu, Holly Kleinschmidt, Jianyu Yang, Erik M Leith, Jenna Johnson, Song Tan, Shaun Mahony, Lu Bai

Abstract read
In one paragraph

Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. The RNA Revolution in the Central Molecular Biology Dogma Evolution.International journal of molecular sciences · 2024
    Review
  12. Review
  13. Pioneer factors: nature or nurture?Critical reviews in biochemistry and molecular biology
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Cheng XuDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA; Center for Eukaryotic Gene Regulation, The Pennsylvania State University, University Park, PA 16802, USA.
Holly KleinschmidtDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA; Center for Eukaryotic Gene Regulation, The Pennsylvania State University, University Park, PA 16802, USA.
Jianyu YangDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA; Center for Eukaryotic Gene Regulation, The Pennsylvania State University, University Park, PA 16802, USA.
Erik M LeithDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA; Center for Eukaryotic Gene Regulation, The Pennsylvania State University, University Park, PA 16802, USA.
Jenna JohnsonDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.
Song TanDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA; Center for Eukaryotic Gene Regulation, The Pennsylvania State University, University Park, PA 16802, USA.
Shaun MahonyDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA; Center for Eukaryotic Gene Regulation, The Pennsylvania State University, University Park, PA 16802, USA.
Lu BaiDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA; Center for Eukaryotic Gene Regulation, The Pennsylvania State University, University Park, PA 16802, USA; Department of Physics, The Pennsylvania State University, University Park, PA 16802, USA. Electronic address: lub15@psu.edu.

Funding

Structural studies of chromatin complexesR35GM127034 · NIGMS · PENNSYLVANIA STATE UNIVERSITY, THE · PI SONG TAN · 2018 to 2026
$4.8M
Mechanism of Chromatin Accessibility, 3D Chromosome Organization, and Their Functions in Gene RegulationR35GM139654 · NIGMS · PENNSYLVANIA STATE UNIVERSITY, THE · PI Lu Bai · 2021 to 2026
$3.8M
Understanding the predeterminants of transcription factor regulatory activityR35GM144135 · NIGMS · PENNSYLVANIA STATE UNIVERSITY, THE · PI Shaun Aengus Mahony · 2022 to 2026
$2.4M
Eukaryotic Gene Regulation (EGR) Predoctoral Training ProgramT32GM125592 · NIGMS · PENNSYLVANIA STATE UNIVERSITY, THE · PI REESE, JOSEPH C · 2018 to 2022
$920k
NIGMS NIH HHS R35 GM127034NIGMS NIH HHS R35 GM139654NIGMS NIH HHS R35 GM144135NIGMS NIH HHS T32 GM125592
6 · The paper itself

Abstract

Despite the unique ability of pioneer factors (PFs) to target nucleosomal sites in closed chromatin, they only bind a small fraction of their genomic motifs. The underlying mechanism of this selectivity is not well understood. Here, we design a high-throughput assay called chromatin immunoprecipitation with integrated synthetic oligonucleotides (ChIP-ISO) to systematically dissect sequence features affecting the binding specificity of a classic PF, FOXA1, in human A549 cells. Combining ChIP-ISO with in vitro and neural network analyses, we find that (1) FOXA1 binding is strongly affected by co-binding transcription factors (TFs) AP-1 and CEBPB; (2) FOXA1 and AP-1 show binding cooperativity in vitro; (3) FOXA1's binding is determined more by local sequences than chromatin context, including eu-/heterochromatin; and (4) AP-1 is partially responsible for differential binding of FOXA1 in different cell types. Our study presents a framework for elucidating genetic rules underlying PF binding specificity and reveals a mechanism for context-specific regulation of its binding.

Indexed as

Hepatocyte Nuclear Factor 3-alphaProtein BindingTranscription Factor AP-1A549 CellsBinding SitesChromatinChromatin ImmunoprecipitationHumansOligonucleotidesChromatinFOXA1 protein, humanHepatocyte Nuclear Factor 3-alphaOligonucleotidesTranscription Factor AP-1binding cooperativitybinding specificityChIP-ISOchromatinpioneer factorsynthetic DNA librarytranscription factor

Identifiers

PMID39019045
PMCPMC11334613

What OpenQuestion holds

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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.