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© The Author(s) 2025. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

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.

Currently, nuclear roles for DVL1 and its involvement in gene regulation remained unclear. Here the authors reveal that altering DVL1 expression significantly reshapes gene expression patterns across the genome and identify ETS1 as a key transcription factor that partners with nuclear DVL1, guiding it to specific genomic targets.

Details

Title
Dishevelled-1 regulates global transcriptomic changes and associates with ETS1 transcription factor
Author
Martinez-Marin, Dalia 1 ; Sharma, Monica 2 ; van Wunnik, Jenna C. 3 ; Sardela de Miranda, Flávia 4   VIAFID ORCID Logo  ; Boligala, Geetha Priya 5 ; Jull, Ella C. 6 ; Stroman, Grace C. 6   VIAFID ORCID Logo  ; Babcock, Rachel L. 5   VIAFID ORCID Logo  ; Pruitt, Kevin 7 

 University of North Carolina, Lineberger Comprehensive Cancer Center, Chapel Hill, USA (ISNI:0000 0004 0452 4880); University of North Carolina, Center for Nanotechnology in Drug Delivery, Chapel Hill, USA (GRID:grid.10698.36) (ISNI:0000 0001 2248 3208) 
 Texas Tech University HSC, Department of Immunology and Molecular Microbiology, Lubbock, USA (GRID:grid.416992.1) (ISNI:0000 0001 2179 3554) 
 Texas Tech University, Department of Biology, Lubbock, USA (GRID:grid.264784.b) (ISNI:0000 0001 2186 7496) 
 Texas Tech University HSC, Department of Cell Biology and Biochemistry, Lubbock, USA (GRID:grid.416992.1) (ISNI:0000 0001 2179 3554); Texas Tech University HSC, Breast Center of Excellence, Lubbock, USA (GRID:grid.416992.1) (ISNI:0000 0001 2179 3554) 
 Texas Tech University HSC, Department of Cell Biology and Biochemistry, Lubbock, USA (GRID:grid.416992.1) (ISNI:0000 0001 2179 3554) 
 University of North Carolina, Department of Pharmacology, Chapel Hill, USA (GRID:grid.10698.36) (ISNI:0000 0001 2248 3208) 
 University of North Carolina, Lineberger Comprehensive Cancer Center, Chapel Hill, USA (GRID:grid.416992.1) (ISNI:0000 0004 0452 4880); University of North Carolina, Department of Pharmacology, Chapel Hill, USA (GRID:grid.10698.36) (ISNI:0000 0001 2248 3208) 
Pages
6288
Publication year
2025
Publication date
2025
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3228184692
Copyright
© The Author(s) 2025. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.