Dishevelled-1 regulates global transcriptomic changes and associates with ETS1 transcription factor

Abstract Dishevelled (DVL) is a crucial component of the Wnt-signaling pathway and is vital for multiple physiological processes. Previously thought to have a classically cytoplasmic role, the discovery of DVL nuclear translocation reframed how it is viewed functionally. Although significant progres...

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Main Authors: Dalia Martinez-Marin, Monica Sharma, Jenna C. van Wunnik, Flávia Sardela de Miranda, Geetha Priya Boligala, Ella C. Jull, Grace C. Stroman, Rachel L. Babcock, Kevin Pruitt
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-61551-1
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author Dalia Martinez-Marin
Monica Sharma
Jenna C. van Wunnik
Flávia Sardela de Miranda
Geetha Priya Boligala
Ella C. Jull
Grace C. Stroman
Rachel L. Babcock
Kevin Pruitt
author_facet Dalia Martinez-Marin
Monica Sharma
Jenna C. van Wunnik
Flávia Sardela de Miranda
Geetha Priya Boligala
Ella C. Jull
Grace C. Stroman
Rachel L. Babcock
Kevin Pruitt
author_sort Dalia Martinez-Marin
collection DOAJ
description Abstract Dishevelled (DVL) is a crucial component of the Wnt-signaling pathway and is vital for multiple physiological processes. Previously thought to have a classically cytoplasmic role, the discovery of DVL nuclear translocation reframed how it is viewed functionally. Although significant progress has been made in understanding the nuclear functions of DVL, further research is required to clarify its roles in transcriptional and epigenetic regulation. A key unresolved question is whether nuclear DVL1 associates with a transcription factor partner. We show here that modulation of DVL1 expression globally affects the transcriptomic landscape. Additionally, analysis of DVL1 ChIP-sequencing allowed us to map genome-wide binding sites, revealing the extensive reach of DVL1 binding. Integration of RNA-sequencing and ChIP-sequencing further revealed ETS1 as a transcription factor binding partner which targets nuclear DVL1 to specific genomic loci. These findings provide insight into the contribution of DVL1 in transcription and clarify aspects of its elusive nuclear function.
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institution Kabale University
issn 2041-1723
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publishDate 2025-07-01
publisher Nature Portfolio
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series Nature Communications
spelling doaj-art-9ab72f6f7e304901a503a4f824317e472025-08-20T03:43:27ZengNature PortfolioNature Communications2041-17232025-07-0116111210.1038/s41467-025-61551-1Dishevelled-1 regulates global transcriptomic changes and associates with ETS1 transcription factorDalia Martinez-Marin0Monica Sharma1Jenna C. van Wunnik2Flávia Sardela de Miranda3Geetha Priya Boligala4Ella C. Jull5Grace C. Stroman6Rachel L. Babcock7Kevin Pruitt8Lineberger Comprehensive Cancer Center, University of North CarolinaDepartment of Immunology and Molecular Microbiology, Texas Tech University HSCDepartment of Biology, Texas Tech UniversityDepartment of Cell Biology and Biochemistry, Texas Tech University HSCDepartment of Cell Biology and Biochemistry, Texas Tech University HSCDepartment of Pharmacology, University of North CarolinaDepartment of Pharmacology, University of North CarolinaDepartment of Cell Biology and Biochemistry, Texas Tech University HSCLineberger Comprehensive Cancer Center, University of North CarolinaAbstract Dishevelled (DVL) is a crucial component of the Wnt-signaling pathway and is vital for multiple physiological processes. Previously thought to have a classically cytoplasmic role, the discovery of DVL nuclear translocation reframed how it is viewed functionally. Although significant progress has been made in understanding the nuclear functions of DVL, further research is required to clarify its roles in transcriptional and epigenetic regulation. A key unresolved question is whether nuclear DVL1 associates with a transcription factor partner. We show here that modulation of DVL1 expression globally affects the transcriptomic landscape. Additionally, analysis of DVL1 ChIP-sequencing allowed us to map genome-wide binding sites, revealing the extensive reach of DVL1 binding. Integration of RNA-sequencing and ChIP-sequencing further revealed ETS1 as a transcription factor binding partner which targets nuclear DVL1 to specific genomic loci. These findings provide insight into the contribution of DVL1 in transcription and clarify aspects of its elusive nuclear function.https://doi.org/10.1038/s41467-025-61551-1
spellingShingle Dalia Martinez-Marin
Monica Sharma
Jenna C. van Wunnik
Flávia Sardela de Miranda
Geetha Priya Boligala
Ella C. Jull
Grace C. Stroman
Rachel L. Babcock
Kevin Pruitt
Dishevelled-1 regulates global transcriptomic changes and associates with ETS1 transcription factor
Nature Communications
title Dishevelled-1 regulates global transcriptomic changes and associates with ETS1 transcription factor
title_full Dishevelled-1 regulates global transcriptomic changes and associates with ETS1 transcription factor
title_fullStr Dishevelled-1 regulates global transcriptomic changes and associates with ETS1 transcription factor
title_full_unstemmed Dishevelled-1 regulates global transcriptomic changes and associates with ETS1 transcription factor
title_short Dishevelled-1 regulates global transcriptomic changes and associates with ETS1 transcription factor
title_sort dishevelled 1 regulates global transcriptomic changes and associates with ets1 transcription factor
url https://doi.org/10.1038/s41467-025-61551-1
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