ArticleThe Journal of biological chemistry2016
Mechanism of Histone H3K4me3 Recognition by the Plant Homeodomain of Inhibitor of Growth 3.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- Breaking barriers: transitioning from X-ray crystallography to cryo-EM for structural studies.Acta crystallographica. Section D, Structural biology · 2026Article
- OverlappING and DivergING roles of ING4 and ING5 in cancer, differentiation and development.Frontiers in cell and developmental biology · 2026Review
- Breaking Barriers: Transitioning from X-ray Crystallography to Cryo-EM for Structural Studies of ATAD2B.bioRxiv : the preprint server for biology · 2025Article
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- The TUDOR domain of SMN is an H3K79Life science alliance · 2023Article
- The chromatin reader protein ING5 is required for normal hematopoietic cell numbers in the fetal liver.Frontiers in immunology · 2023Article
- SMA-linked SMN mutants prevent phase separation properties and SMN interactions with FMRP family members.Life science alliance · 2023Article
- Structural insight into ASH1L PHD finger recognizing methylated histone H3K4 and promoting cell growth in prostate cancer.Frontiers in oncology · 2022Article
- AnPeerJ · 2022Article
- A Novel Splice Variant of the Inhibitor of Growth 3 Lacks the Plant Homeodomain and Regulates Epithelial-Mesenchymal Transition in Prostate Cancer Cells.Biomolecules · 2021Article
- Aberrant Activity of Histone-Lysine N-Methyltransferase 2 (KMT2) Complexes in Oncogenesis.International journal of molecular sciences · 2020Review
- Understanding the interplay between CpG island-associated gene promoters and H3K4 methylation.Biochimica et biophysica acta. Gene regulatory mechanisms · 2020Review
- Downregulation of nuclear ING3 expression and translocalization to cytoplasm promotes tumorigenesis and progression in head and neck squamous cell carcinoma (HNSCC).Histology and histopathology · 2020Article
- Molecular Structure, Binding Affinity, and Biological Activity in the Epigenome.International journal of molecular sciences · 2020Review
- Epigenetic reader complexes of the human malaria parasite, Plasmodium falciparum.Nucleic acids research · 2019Article
- ING3 is required for ATM signaling and DNA repair in response to DNA double strand breaks.Cell death and differentiation · 2019Article
- The many lives of KATs - detectors, integrators and modulators of the cellular environment.Nature reviews. Genetics · 2019Review
- Human ex vivo prostate tissue model system identifies ING3 as an oncoprotein.British journal of cancer · 2018Article
- Biological function and histone recognition of family IV bromodomain-containing proteins.Journal of cellular physiology · 2018Review
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Aberrant access to genetic information disrupts cellular homeostasis and can lead to cancer development. One molecular mechanism that regulates access to genetic information includes recognition of histone modifications, which is carried out by protein modules that interact with chromatin and serve as landing pads for enzymatic activities that regulate gene expression. The ING3 tumor suppressor protein contains a plant homeodomain (PHD) that reads the epigenetic code via recognition of histone H3 tri-methylated at lysine 4 (H3K4me3), and this domain is lost or mutated in various human cancers. However, the molecular mechanisms targeting ING3 to histones and the role of this interaction in the cell remain elusive. Thus, we employed biochemical and structural biology approaches to investigate the interaction of the ING3 PHD finger (ING3PHD) with the active transcription mark H3K4me3. Our results demonstrate that association of the ING3PHD with H3K4me3 is in the sub-micromolar range (KD ranging between 0.63 and 0.93 μm) and is about 200-fold stronger than with the unmodified histone H3. NMR and computational studies revealed an aromatic cage composed of Tyr-362, Ser-369, and Trp-385 that accommodate the tri-methylated side chain of H3K4. Mutational analysis confirmed the critical importance of Tyr-362 and Trp-385 in mediating the ING3PHD-H3K4me3 interaction. Finally, the biological relevance of ING3PHD-H3K4me3 binding was demonstrated by the failure of ING3PHD mutant proteins to enhance ING3-mediated DNA damage-dependent cell death. Together, our results reveal the molecular mechanism of H3K4me3 selection by the ING3PHD and suggest that this interaction is important for mediating ING3 tumor suppressive activities.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.