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Updated: Aug 5, 2026

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09:58

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Perturb-seq reveals TCF7 as a transcriptional link between MAPK- and Wnt-driven gene expression

Ghanem El Kassem1, Anja Sieber2, Bertram Klinger2

  • 1Institute of Molecular Medicine, Section for Molecular Medicine of Signal Transduction, Faculty of Medicine, Martin-Luther-University Halle-Wittenberg, 06120 Halle (Saale), Germany.

Nucleic Acids Research
|July 29, 2026
PubMed

Insights

This study reveals how the RAF-MAPK pathway controls gene expression through key transcription factors like EGR1 and FOS. It also uncovers a link between MAPK and Wnt signaling via TCF7, impacting disease.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Systems Biology

Background:

  • The mitogen-activated protein kinase (MAPK) pathway is crucial in cell signaling and disease.
  • Understanding how MAPK activation drives transcriptional changes is essential but incomplete.

Purpose of the Study:

  • To map target gene sets of RAF-MAPK pathway transcription factors.
  • To elucidate the network architecture of MAPK-driven gene regulation.
  • To identify cross-talk between MAPK and other signaling pathways.

Main Methods:

  • Targeted Perturb-seq was used to map gene sets for 22 RAF-inducible transcription factors.
  • Time-resolved transcriptional profiling was integrated with network reconstruction.

Main Results:

  • EGR1 and FOS were identified as central hubs co-regulating target gene sets.
  • A positive feedback loop between EGR1 and TCF7 was discovered.
  • TCF7 acts as a link integrating MAPK and Wnt pathway signals.

Conclusions:

  • The study defines the transcriptional network architecture of RAF-MAPK signaling.
  • Cross-talk between oncogenic pathways is encoded within transcriptional networks.
  • TCF7 plays a key role in integrating signals from MAPK and Wnt pathways.

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