ArticleCell genomics2025
Interpreting regulatory mechanisms of Hippo signaling through a deep learning sequence model.
Article in Cell genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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Who cites it
8 citing papers in PubMed.
- AlphaGenome Atlas:medRxiv : the preprint server for health sciences · 2026Article
- Positional interpretation of cis-regulatory code and nucleosome organization with deep learning models.Nature communications · 2026Article
- iDualG4: A Dual-Channel Deep Learning Framework for Predicting In Vivo G-Quadruplexes.Biomolecules · 2026Article
- TEAD4 and RXRA Regulate the Function of Nucleus Pulposus Cells in Intervertebral Disc Degeneration Via the TNF-α/NF-κB Pathway: An Integrated Analysis of Single-Cell RNA-Seq, Bulk RNA-Seq, and In Vitro Validation.Applied biochemistry and biotechnology · 2026Article
- Review
- Widespread low-affinity motifs enhance chromatin accessibility and regulatory potential in mESCs.bioRxiv : the preprint server for biology · 2025Article
- Uncovering the Mechanistic Landscape of Regulatory DNA with Deep Learning.bioRxiv : the preprint server for biology · 2025Article
- Chromatin-dependent motif syntax defines differentiation trajectories.Molecular cell · 2025Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Signaling pathway components are well studied, but how they mediate cell-type-specific transcription responses is an unresolved problem. Using the Hippo pathway in mouse trophoblast stem cells as a model, we show that the DNA binding of signaling effectors is driven by cell-type-specific sequence rules that can be learned genome wide by deep learning models. Through model interpretation and experimental validation, we show that motifs for the cell-type-specific transcription factor TFAP2C enhance TEAD4/YAP1 binding in a nucleosome-range and distance-dependent manner, driving synergistic enhancer activation. We also discovered that Tead double motifs are widespread, highly active canonical response elements. Molecular dynamics simulations suggest that TEAD4 binds them cooperatively through surprisingly labile protein-protein interactions that depend on the DNA template. These results show that the response to signaling pathways is encoded in the cis-regulatory sequences and that interpreting the rules reveals insights into the mechanisms by which signaling effectors influence cell-type-specific enhancer activity.
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Registered trials
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 Socratic graph.