GO:0062060 NuA4 histone acetyltransferase complex binding: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0062060 (NuA4 histone acetyltransferase complex binding) is a molecular function describing the selective binding of a protein to the NuA4 histone acetyltransferase complex.
• The NuA4 complex is a conserved multisubunit assembly that acetylates histone H4 and H2A, and in humans is known as the TIP60 complex.
• Structural studies have revealed how NuA4 subunits recognize nucleosomes and how the complex is organized around a catalytic HAT module.
• Binding to NuA4 is often mediated by dedicated adaptor or targeting subunits, such as Eaf1 in yeast, which links the complex to Htz1 incorporation and purine biosynthesis.
• The NPAS4-NuA4 interaction couples synaptic activity to DNA repair, illustrating how NuA4 binding can be signal-dependent and neuron-specific.
• Research on GO:0062060 benefits from CRISPR knockout, knock-in, and overexpression models combined with structural, proteomic, and genomic assays.
Description
GO:0062060, NuA4 histone acetyltransferase complex binding, is a molecular function term that describes the binding of a protein or biomolecule to the NuA4 histone acetyltransferase complex. The NuA4 complex is a conserved chromatin-modifying machine that acetylates histone H4 and H2A, thereby influencing transcription, DNA repair, and genome stability. In humans, the complex is often referred to as the TIP60 complex, and its subunits are implicated in a wide range of nuclear processes. Understanding what binds to NuA4, and how, is therefore central to understanding how chromatin states are established and remodeled. The term is experimentally defined by assays that detect physical association between a candidate protein and the intact NuA4 complex, such as affinity purification, co-immunoprecipitation, or structural determination of NuA4 in complex with its binding partners. Recent cryo-electron microscopy studies have provided near-atomic models of yeast and human NuA4, revealing the architecture of the complex and the surfaces available for interaction with nucleosomes and regulatory proteins. These structures help explain how binding events can target NuA4 to specific genomic loci and how they modulate its acetyltransferase activity. For researchers, GO:0062060 is a useful annotation because it distinguishes proteins that directly engage the NuA4 complex from those that merely act in the same pathway. The term is particularly relevant in neurobiology, where the NPAS4-NuA4 interaction links synaptic activity to DNA repair, and in yeast biology, where Eaf1 connects NuA4 to Htz1 deposition and metabolic regulation. This article reviews the definition, mechanism, key genes, disease links, and experimental approaches for studying NuA4 histone acetyltransferase complex binding.
NuA4 histone acetyltransferase complex binding At A Glance
| GO ID | GO:0062060 |
|---|---|
| GO term | NuA4 histone acetyltransferase complex binding |
| Ontology | molecular_function |
| Synonym | None listed |
| Definition | Binding to a NuA4 histone acetyltransferase complex. |
| Major function | Physical association with the NuA4/TIP60 histone acetyltransferase complex, often to target or regulate its chromatin-modifying activity. |
| Example interactor | Eaf1 in yeast links NuA4 to Htz1 incorporation and purine biosynthesis. |
| Human complex | TIP60 complex, a NuA4-related assembly with roles in transcription and DNA repair. |
| Structural basis | Cryo-EM structures of yeast and human NuA4 reveal subunit organization and nucleosome-binding interfaces. |
What Is GO:0062060?
In simple terms, GO:0062060 describes the act of a protein sticking to the NuA4 histone acetyltransferase complex. The official definition is binding to a NuA4 histone acetyltransferase complex. This is a molecular function annotation: it is assigned to the protein that does the binding, not to the NuA4 complex itself. The NuA4 complex is a multi-subunit assembly that acetylates histones, and proteins annotated with GO:0062060 are those that physically associate with this complex, often to regulate its localization, substrate selection, or activity.
Why Is NuA4 histone acetyltransferase complex binding Important in Cell Biology?
GO:0062060 matters because the NuA4 complex sits at the intersection of chromatin regulation, transcription, and genome maintenance, and its binding partners determine where and when these activities occur. Defects in NuA4 subunits or their interactors are linked to cancer, neurodevelopmental disorders, and impaired DNA repair, making the study of NuA4 binding directly relevant to human health. Moreover, the term provides a precise annotation for functional genomics and proteomics, helping researchers distinguish direct physical interactions from indirect pathway relationships.
• NuA4 binding proteins can target the complex to specific promoters or enhancers, shaping transcriptional programs.
• The NPAS4-NuA4 interaction couples neuronal activity to DNA repair, linking GO:0062060 to synaptic plasticity and neuroprotection.
• Eaf1-mediated binding connects NuA4 to Htz1 incorporation and purine biosynthesis in yeast, showing metabolic roles.
• Structural studies of NuA4 bound to nucleosomes reveal how binding surfaces control histone acetylation.
• Human TIP60 complex dysfunction is associated with cancer and genomic instability, highlighting clinical relevance.
• GO:0062060 annotations help interpret proteomic interaction networks and CRISPR screens.
• The term supports mechanistic studies of chromatin remodelers and histone exchange.
• Understanding NuA4 binding can inform drug discovery targeting epigenetic regulators.
Molecular Mechanism of NuA4 histone acetyltransferase complex binding
Recognition of the NuA4 complex surface
In simple terms: Binding starts when a protein finds a compatible surface on the NuA4 complex.
Structural studies of yeast and human NuA4 have revealed the overall architecture of the complex and the surfaces that are available for protein-protein interactions. The catalytic HAT module is embedded within a scaffold of subunits, and binding partners typically engage exposed regions of this scaffold rather than the active site itself. In yeast, Eaf1 serves as a key subunit that links NuA4 to downstream processes, and its interaction surfaces are important for recruiting the complex to specific targets. These structural insights provide a framework for understanding how proteins annotated with GO:0062060 achieve specificity.
Nucleosome-associated binding and substrate engagement
In simple terms: Some binding events happen while NuA4 is already sitting on a nucleosome.
NuA4 binds nucleosomes to acetylate histone H4 and H2A, and structural studies have captured the complex in nucleosome-bound states. The Piccolo NuA4 subcomplex recognizes nucleosomes with high affinity, and this recognition is a prerequisite for efficient acetylation. Proteins that bind the NuA4 complex may do so in the context of chromatin, potentially stabilizing or altering nucleosome engagement. This layer of regulation helps ensure that acetylation occurs at appropriate genomic locations.
Signal-dependent recruitment: the NPAS4-NuA4 example
In simple terms: In neurons, a activity-induced protein called NPAS4 binds NuA4 to trigger DNA repair.
The transcription factor NPAS4 forms a complex with NuA4 in neurons, coupling synaptic activity to DNA repair. This interaction is a clear example of regulated binding to the NuA4 complex, where the binding partner is itself induced by neuronal activity. The NPAS4-NuA4 complex functions in DNA double-strand break repair, linking GO:0062060 to activity-dependent genome maintenance. This finding illustrates how NuA4 binding can be context-specific and physiologically important.
Regulation by complex composition and post-translational modifications
In simple terms: The exact subunits present in NuA4 can change what it binds and how it behaves.
The NuA4 complex exists in different forms, including the full complex and the smaller Piccolo NuA4 subcomplex, which differ in subunit composition and nucleosome recognition properties. Structural flexibility in the yeast NuA4 complex suggests that conformational changes may regulate access to binding surfaces. Post-translational modifications of NuA4 subunits or their binding partners could further modulate interactions, although specific modifications are still being mapped. Together, these layers of regulation determine when and where GO:0062060 activity occurs.
Key Genes Involved in GO:0062060 NuA4 histone acetyltransferase complex binding
The following genes and proteins are central to the study of NuA4 histone acetyltransferase complex binding, based on structural, biochemical, and genetic evidence.
| Gene | Major Role | Research Relevance |
|---|---|---|
| EP400 | Catalytic ATPase/helicase subunit of human NuA4/TIP60 complex | Structural and functional studies of human NuA4 |
| KAT5 (TIP60) | Histone acetyltransferase catalytic subunit | Core enzymatic activity and cancer relevance |
| TRRAP | Scaffold subunit shared with other HAT complexes | Complex assembly and interaction platform |
| EPC1 | Subunit of human NuA4/TIP60 complex | Structural integrity and nucleosome binding |
| EPC2 | Subunit of human NuA4/TIP60 complex | Complex assembly and function |
| VPS72 (YL1) | Histone chaperone-like subunit | Nucleosome interaction and histone exchange |
| YEATS4 | Subunit with YEATS domain | Chromatin targeting and structural studies |
| DMAP1 | Subunit of NuA4/TIP60 complex | Transcriptional regulation and complex stability |
| RUVBL1 | AAA+ ATPase subunit | Complex assembly and remodeling |
| RUVBL2 | AAA+ ATPase subunit | Complex assembly and remodeling |
| ACTL6A | Actin-related protein subunit | Structural integrity and chromatin remodeling |
| EAF1 | Yeast subunit linking NuA4 to Htz1 and purine biosynthesis | Genetic and biochemical studies of NuA4 targeting |
| EAF3 | Yeast subunit with chromodomain | Nucleosome recognition and binding |
| EAF5 | Yeast subunit of Piccolo NuA4 | Nucleosome binding studies |
| EAF6 | Yeast subunit of Piccolo NuA4 | Nucleosome binding studies |
| ESA1 | Yeast histone acetyltransferase catalytic subunit | Enzymatic activity and structural studies |
| NPAS4 | Neuron-specific transcription factor that binds NuA4 | Activity-dependent DNA repair |
How Is NuA4 histone acetyltransferase complex binding Regulated?
Binding to the NuA4 complex is regulated at multiple levels. In neurons, NPAS4 expression is induced by synaptic activity, and the resulting NPAS4-NuA4 interaction couples activity to DNA repair. In yeast, Eaf1 links NuA4 to Htz1 incorporation and purine biosynthesis, suggesting metabolic and chromatin-related regulation. The composition of the complex itself, including the presence of the Piccolo NuA4 subcomplex, influences nucleosome recognition and binding properties. Structural flexibility observed in the yeast NuA4 complex may allow conformational changes that regulate access to binding surfaces. Post-translational modifications of NuA4 subunits or their partners are likely to add further layers of control, although specific regulatory modifications remain an active area of research.
NuA4 histone acetyltransferase complex binding and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| KAT5 (TIP60) | Cancer, DNA repair defects | CRISPR knockout in cancer cell lines |
| EP400 | Cancer, chromatin remodeling | Knock-in of patient mutations |
| NPAS4 | Neurodevelopmental disorders, synaptic dysfunction | Neuron-specific knockout or overexpression |
| EAF1 | Metabolic regulation (yeast model) | Yeast knockout and point mutants |
| TRRAP | Cancer, transcriptional dysregulation | CRISPR knockout in human cells |
Cancer and genomic instability
The human NuA4/TIP60 complex, including its catalytic subunit KAT5 (TIP60), is frequently altered in cancer, and its roles in DNA repair and transcription make it a tumor suppressor candidate. Proteins that bind NuA4 could influence cancer risk by modulating complex localization or activity. Structural studies of the human complex provide a basis for understanding how mutations in binding interfaces might contribute to disease.
Neurodevelopmental and neurodegenerative disorders
The NPAS4-NuA4 interaction is critical for activity-dependent DNA repair in neurons, and disruption of this pathway may contribute to neurodevelopmental or neurodegenerative conditions. NPAS4 is a neuron-specific transcription factor, and its binding to NuA4 links synaptic activity to genome maintenance. This connection suggests that GO:0062060-related mechanisms are relevant to brain health and disease.
Metabolic and chromatin-related disorders
In yeast, Eaf1-mediated binding of NuA4 to Htz1 incorporation and purine biosynthesis reveals a link between chromatin regulation and metabolism. While direct human disease associations are less clear, these findings suggest that NuA4 binding proteins could influence metabolic pathways. Further research is needed to translate these yeast observations to human disease.
From NuA4 histone acetyltransferase complex binding-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does a candidate protein directly bind NuA4? | Knock-in of epitope-tagged candidate followed by affinity purification |
| What is the functional consequence of losing NuA4 binding? | CRISPR knockout of the binding protein or binding interface |
| How does a disease-associated mutation affect NuA4 binding? | Point mutation knock-in of the mutation |
| Can overexpression of a binding partner alter chromatin state? | Overexpression cell models |
| What is the structural basis of binding? | Recombinant expression and cryo-EM |
| Which genes are required for NuA4 recruitment? | CRISPR library screening |
How to Study the NuA4 histone acetyltransferase complex binding Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Affinity purification-mass spectrometry | Physical interactions with NuA4 | Identifying new binding partners |
| Cryo-EM | 3D structure of NuA4 and bound proteins | Mapping binding interfaces |
| ChIP-seq | Genomic localization of NuA4 | Linking binding to chromatin targets |
| Co-immunoprecipitation | In vivo complex formation | Validating interactions |
| DNA repair assays | Functional DNA repair capacity | Testing NPAS4-NuA4 role |
| RNA-seq | Transcriptional changes | Assessing consequences of binding loss |
| Yeast genetics | Growth and metabolic phenotypes | Studying Eaf1 function |
| Nucleosome binding assays | Affinity for nucleosomes | Piccolo NuA4 studies |
Affinity purification and mass spectrometry
Affinity purification of NuA4 subunits followed by mass spectrometry is a standard approach to identify binding partners. This method can detect stable interactions and is often combined with crosslinking to capture transient associations. Structural studies have used purified complexes to define subunit composition and interfaces.
Structural biology (cryo-EM and crystallography)
Cryo-electron microscopy has been used to determine the structures of yeast and human NuA4 complexes, including nucleosome-bound states. These structures reveal the surfaces available for binding and how subunits are organized. Structural data are essential for interpreting the functional consequences of mutations in binding interfaces.
Genomic and proteomic profiling
Chromatin immunoprecipitation followed by sequencing (ChIP-seq) can map where NuA4 and its binding partners localize across the genome. Proteomic approaches can quantify changes in complex composition under different conditions. These methods help link binding events to transcriptional and repair outcomes.
Functional assays for DNA repair and transcription
DNA repair assays, including double-strand break repair reporters, can test the functional importance of NuA4 binding. Transcriptional reporters and RNA-seq can assess changes in gene expression upon loss or gain of binding. These assays connect molecular binding to cellular phenotypes.
How CRISPR Can Be Used to Study GO:0062060 NuA4 histone acetyltransferase complex binding
Knockout
CRISPR knockout of genes encoding NuA4 subunits or their binding partners can reveal the functional importance of the interaction. For example, knocking out NPAS4 in neurons abolishes the NPAS4-NuA4 interaction and impairs activity-dependent DNA repair. Knockout of yeast EAF1 affects Htz1 incorporation and purine biosynthesis. These models are essential for causal inference.
Point Mutation
Point mutations can be introduced into binding interfaces to test specificity without deleting the entire protein. For instance, mutations in the NuA4 subunit surfaces identified by cryo-EM can be tested for loss of binding. This approach is valuable for dissecting disease-associated variants.
Knock-in
Knock-in of epitope tags or fluorescent proteins allows for direct visualization and purification of NuA4 complexes. Tagged knock-in models can be used in co-immunoprecipitation and imaging experiments. This strategy preserves endogenous regulation of expression.
Overexpression
Overexpression of a binding partner can drive excess complex formation and reveal dominant phenotypes. For example, overexpression of NPAS4 may enhance NuA4 recruitment to activity-dependent sites. Overexpression models are useful for gain-of-function studies.
How EDITGENE Supports NuA4 histone acetyltransferase complex binding Research
Researchers studying NuA4 histone acetyltransferase complex binding-related genes often need to determine whether a candidate gene is causally involved in complex assembly, targeting, or function. EDITGENE provides a comprehensive suite of CRISPR-based services to generate precisely engineered cell models for such studies.
Contact EDITGENE today to design your custom CRISPR model for NuA4 histone acetyltransferase complex binding research.
Frequently Asked Questions About NuA4 histone acetyltransferase complex binding
What is GO:0062060?
GO:0062060 is a Gene Ontology molecular function term defined as binding to a NuA4 histone acetyltransferase complex.
What is the NuA4 histone acetyltransferase complex?
The NuA4 complex is a conserved multisubunit chromatin-modifying assembly that acetylates histones H4 and H2A, with the human version known as TIP60.
What genes are involved in NuA4 histone acetyltransferase complex binding?
Key genes include EP400, KAT5 (TIP60), TRRAP, EPC1, EPC2, VPS72, YEATS4, DMAP1, RUVBL1, RUVBL2, ACTL6A, and in yeast EAF1, EAF3, EAF5, EAF6, and ESA1.
How is NuA4 binding studied experimentally?
Common methods include affinity purification-mass spectrometry, cryo-EM, co-immunoprecipitation, ChIP-seq, and CRISPR-based knockouts.
What diseases are linked to NuA4 binding?
NuA4/TIP60 dysfunction is linked to cancer and genomic instability, and the NPAS4-NuA4 interaction is important for neuronal DNA repair.
What is the role of NPAS4 in NuA4 binding?
NPAS4 is a neuron-specific transcription factor that binds NuA4 to couple synaptic activity to DNA repair.
How does Eaf1 relate to NuA4 binding?
Eaf1 is a yeast NuA4 subunit that links the complex to Htz1 incorporation and purine biosynthesis.
What structural information is available for NuA4?
Cryo-EM structures of yeast and human NuA4, including nucleosome-bound states, have been determined.
Can CRISPR be used to study NuA4 binding?
Yes, CRISPR knockout, knock-in, and point mutation models are widely used to dissect NuA4 interactions.
What is the Piccolo NuA4 complex?
Piccolo NuA4 is a subcomplex of NuA4 that recognizes nucleosomes and is involved in histone acetylation.
Conclusion
GO:0062060, NuA4 histone acetyltransferase complex binding, captures a critical molecular function that underlies chromatin regulation, transcription, and DNA repair. Structural and functional studies have illuminated how proteins bind the NuA4/TIP60 complex and how these interactions are regulated. Understanding these binding events provides insight into cancer, neurobiology, and metabolic regulation, and offers opportunities for therapeutic intervention. Continued research using CRISPR models and advanced structural techniques will further clarify the roles of NuA4 binding partners in health and disease.
References
- 1. Yang Z et al.. 2024. Structural insights into the human NuA4/TIP60 acetyltransferase and chromatin remodeling complex.. Science 385(6711):eadl5816 PMID: 39088653
- 2. Ji L et al.. 2022. Structure of the NuA4 histone acetyltransferase complex.. Proc Natl Acad Sci U S A 119(48):e2214313119 PMID: 36417436
- 3. Pollina EA et al.. 2023. A NPAS4-NuA4 complex couples synaptic activity to DNA repair.. Nature 614(7949):732-741 PMID: 36792830
- 4. Zukin SA et al.. 2022. Structure and flexibility of the yeast NuA4 histone acetyltransferase complex.. Elife 11 PMID: 36263929
- 5. Li C et al.. 2024. Structure of the human TIP60-C histone exchange and acetyltransferase complex.. Nature 635(8039):764-769 PMID: 39260417
- 6. Qu K et al.. 2022. Structure of the NuA4 acetyltransferase complex bound to the nucleosome.. Nature 610(7932):569-574 PMID: 36198799
- 7. Cheng X et al.. 2015. Eaf1 Links the NuA4 Histone Acetyltransferase Complex to Htz1 Incorporation and Regulation of Purine Biosynthesis.. Eukaryot Cell 14(6):535-44 PMID: 25841019
- 8. Berndsen CE et al.. 2007. Nucleosome recognition by the Piccolo NuA4 histone acetyltransferase complex.. Biochemistry 46(8):2091-9 PMID: 17274630
