PUBLICATION
The TRIP12 E3 ligase induces SWI/SNF component BRG1-β-catenin interaction to promote Wnt signaling
- Authors
- Kassel, S., Yuan, K., Bunnag, N., Neitzel, L.R., Lu, W., Schwarzkopf, A., Maines, B., Loberg, M.A., Xu, G., Adams, A., McCray, A.D., Cho, A., Rockouski, M., Orton, G., Goldsmith, L., Aronno, M.M.A., Spencer, Z.T., Khan, O.M., Ye, F., Williams, C., Lebensohn, A.M., Rohatgi, R., Wang, X., Weiss, V.L., Hong, C.C., Kettenbach, A.N., Robbins, D.J., Ahmed, Y., Lee, E.
- ID
- ZDB-PUB-250606-2
- Date
- 2025
- Source
- Nature communications 16: 52485248 (Journal)
- Registered Authors
- Hong, Charles
- Keywords
- none
- MeSH Terms
-
- Ubiquitin-Protein Ligases*/genetics
- Ubiquitin-Protein Ligases*/metabolism
- Protein Binding
- Nuclear Proteins*/genetics
- Nuclear Proteins*/metabolism
- Animals
- beta Catenin*/genetics
- beta Catenin*/metabolism
- HEK293 Cells
- DNA Helicases*/genetics
- DNA Helicases*/metabolism
- Ubiquitination
- Mice
- Transcription Factors*/genetics
- Transcription Factors*/metabolism
- Wnt Signaling Pathway*
- Humans
- Zebrafish
- PubMed
- 40473626 Full text @ Nat. Commun.
Citation
Kassel, S., Yuan, K., Bunnag, N., Neitzel, L.R., Lu, W., Schwarzkopf, A., Maines, B., Loberg, M.A., Xu, G., Adams, A., McCray, A.D., Cho, A., Rockouski, M., Orton, G., Goldsmith, L., Aronno, M.M.A., Spencer, Z.T., Khan, O.M., Ye, F., Williams, C., Lebensohn, A.M., Rohatgi, R., Wang, X., Weiss, V.L., Hong, C.C., Kettenbach, A.N., Robbins, D.J., Ahmed, Y., Lee, E. (2025) The TRIP12 E3 ligase induces SWI/SNF component BRG1-β-catenin interaction to promote Wnt signaling. Nature communications. 16:52485248.
Abstract
SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complexes displace nucleosomes to promote the access of transcription factors to enhancers and promoters. Despite the critical roles of SWI/SNF in animal development and tumorigenesis, how signaling pathways recruit SWI/SNF complexes to their target genes is unclear. Here, we demonstrate that target gene activation mediated by β-catenin, the essential transcriptional coactivator in the Wnt signal transduction pathway, requires ubiquitylation of the SWI/SNF component Brahma-related gene-1 (BRG1) by the E3 ubiquitin ligase Thyroid Hormone Receptor Interactor 12 (TRIP12). TRIP12 depletion in Drosophila, zebrafish, mouse organoids, and human cells attenuates Wnt signaling. Genetic epistasis experiments place TRIP12 activity downstream of the β-catenin destruction complex. TRIP12 interacts with and ubiquitylates BRG1, and BRG1 depletion blocks TRIP12-mediated Wnt pathway activation. TRIP12 promotes BRG1 binding to β-catenin in the presence of Wnt. Our findings support a model in which TRIP12 ubiquitylates BRG1 in the presence of Wnt and promotes its interaction with β-catenin in the nucleus, in order to recruit SWI/SNF to Wnt target genes. Our studies suggest a general mechanism by which cell signaling induces the interaction between BRG1 and pathway-specific transcription factors to recruit SWI/SNF complexes to their appropriate target genes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping