ArticleJournal of molecular biology2010
Allosteric remodelling of the histone H3 binding pocket in the Pygo2 PHD finger triggered by its binding to the B9L/BCL9 co-factor.
Article in Journal of molecular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- PYGO1 drives gastric cancer progression via the ITGB1/CD47 axis and is therapeutically targeted by pentagalloylglucose.Journal of translational medicine · 2025Article
- Pygo-F773W Mutation Reveals Novel Functions beyond Wnt Signaling inInternational journal of molecular sciences · 2024Article
- The Wnt-dependent and Wnt-independent functions of BCL9 in development, tumorigenesis, and immunity: Implications in therapeutic opportunities.Genes & diseases · 2024Review
- Dissecting the molecular basis for the modulation of neurotransmitter GPCR signaling by GINIP.Structure (London, England : 1993) · 2024Article
- Dissecting the molecular basis for the modulation of neurotransmitter GPCR signaling by GINIP.bioRxiv : the preprint server for biology · 2023Article
- Endometrial epithelial cells-derived exosomes deliver microRNA-30c to block the BCL9/Wnt/CD44 signaling and inhibit cell invasion and migration in ovarian endometriosis.Cell death discovery · 2022Article
- The WNT/β-catenin dependent transcription: A tissue-specific business.WIREs mechanisms of disease · 2021Review
- The structural biology of canonical Wnt signalling.Biochemical Society transactions · 2020Review
- Targeting epigenetic protein-protein interactions with small-molecule inhibitors.Future medicinal chemistry · 2020Review
- Kinase inhibition profiles as a tool to identify kinases for specific phosphorylation sites.Nature communications · 2020Article
- BCL9 provides multi-cellular communication properties in colorectal cancer by interacting with paraspeckle proteins.Nature communications · 2020Article
- USP9X-mediated deubiquitination of B-cell CLL/lymphoma 9 potentiates Wnt signaling and promotes breast carcinogenesis.The Journal of biological chemistry · 2019Article
- Bcl9 and Pygo synergise downstream of Apc to effect intestinal neoplasia in FAP mouse models.Nature communications · 2019Article
- Expression of miR-30c and BCL-9 in gastric carcinoma tissues and their function in the development of gastric cancer.Oncology letters · 2018Article
- KDM3 epigenetically controls tumorigenic potentials of human colorectal cancer stem cells through Wnt/β-catenin signalling.Nature communications · 2017Article
- Logical design of an anti-cancer agent targeting the plant homeodomain in Pygopus2.Cancer science · 2016Article
- A Structural Perspective on Readout of Epigenetic Histone and DNA Methylation Marks.Cold Spring Harbor perspectives in biology · 2016Review
- The evolving roles of canonical WNT signaling in stem cells and tumorigenesis: implications in targeted cancer therapies.Laboratory investigation; a journal of technical methods and pathology · 2016Article
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Authors and funding
5 authors.
Funding
Abstract
The Zn-coordinated PHD fingers of Pygopus (Pygo) proteins are critical for beta-catenin-dependent transcriptional switches in normal and malignant tissues. They bind to methylated histone H3 tails, assisted by their BCL9 co-factors whose homology domain 1 (HD1) binds to the rear PHD surface. Although histone-binding residues are identical between the two human Pygo paralogs, we show here that Pygo2 complexes exhibit slightly higher binding affinities for methylated histone H3 tail peptides than Pygo1 complexes. We solved the crystal structure of the Pygo2 PHD-BCL9-2 HD1 complex, which revealed paralog-specific interactions in its PHD-HD1 interface that could contribute indirectly to its elevated affinity for the methylated histone H3 tail. Interestingly, using NMR spectroscopy, we discovered that HD1 binding to PHD triggers an allosteric communication with a conserved isoleucine residue that lines the binding channel for histone H3 threonine 3 (T3), the link between the two adjacent binding pockets accommodating histone H3 alanine 1 and methylated lysine 4, respectively. This modulates the surface of the T3 channel, providing a plausible explanation as to how BCL9 co-factors binding to Pygo PHD fingers impact indirectly on their histone binding affinity. Intriguingly, this allosteric modulation of the T3 channel is propagated through the PHD structural core by a highly conserved tryptophan, the signature residue defining the PHD subclass of Zn fingers, which suggests that other PHD proteins may also be assisted by co-factors in their decoding of modified histone H3 tails.
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