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Updated: May 1, 2026

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
Published on: July 25, 2019
The forkhead transcription factor FOXK2 acts as a chromatin targeting factor for the BAP1-containing histone
Zongling Ji1, Hisham Mohammed2, Aaron Webber1
1Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
Abstract:
There are numerous forkhead transcription factors in mammalian cells but we know little about the molecular functions of the majority of these. FOXK2 is a ubiquitously expressed family member suggesting an important function across multiple cell types. Here, we show that FOXK2 binds to the SIN3A and PR-DUB complexes. The PR-DUB complex contains the important tumour suppressor protein, the deubiquitinase BAP1. FOXK2 recruits BAP1 to DNA, promotes local histone deubiquitination and causes changes in target gene activity. Our results therefore provide an important link between BAP1 and the transcription factor FOXK2 and demonstrate how BAP1 can be recruited to specific regulatory loci.
Insights
The forkhead transcription factor FOXK2 binds to the tumor suppressor BAP1 complex, recruiting it to DNA. This interaction promotes histone deubiquitination and alters gene activity, revealing a novel regulatory mechanism.
Area of Science:
- Molecular Biology
- Genetics
- Epigenetics
Background:
- Mammalian cells possess numerous forkhead transcription factors with largely unknown molecular functions.
- FOXK2 is a widely expressed transcription factor, indicating a significant role across various cell types.
Purpose of the Study:
- To elucidate the molecular function of the FOXK2 transcription factor.
- To investigate the interaction between FOXK2 and the PR-DUB complex, which includes the tumor suppressor BAP1.
Main Methods:
- Co-immunoprecipitation assays to detect protein-protein interactions.
- Chromatin immunoprecipitation to assess DNA binding.
- Analysis of gene expression changes and histone modifications.
Main Results:
- FOXK2 was found to bind to the SIN3A and PR-DUB complexes.
- FOXK2 facilitates the recruitment of BAP1 (a deubiquitinase and tumor suppressor) to DNA.
- This recruitment leads to localized histone deubiquitination and subsequent alterations in target gene activity.
Conclusions:
- Established a significant link between the transcription factor FOXK2 and the tumor suppressor BAP1.
- Demonstrated a mechanism by which BAP1 is recruited to specific DNA regulatory regions via FOXK2.
- Highlighted the role of FOXK2 in regulating gene activity through BAP1-mediated epigenetic modifications.
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