GO:0000123 histone acetyltransferase complex: Components, Assembly and Research Methods, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0000123 (histone acetyltransferase complex) is a cellular component defined as a protein complex that possesses histone acetyltransferase activity [QuickGO].
• Major complexes include Hat1-Hat2, NuA3, NuA4, SAGA, and ATAC, which acetylate histone H3 and H4 to regulate chromatin accessibility and transcription [3,6,7,8].
• Structural studies reveal distinct modules for histone recognition and catalysis, such as the NuA4 core and SAGA HAT module [3,6].
• Dysregulation of HAT complexes is linked to cancer, developmental disorders, and metabolic diseases [1,4].
• CRISPR knockout, point mutation, knock-in, and overexpression models are essential to dissect subunit-specific functions [4,5].
• EDITGENE provides custom cell models and screening services to study histone acetyltransferase complexes.
Description
The histone acetyltransferase complex (GO:0000123) is a cellular component defined by its ability to acetylate histone proteins, a key epigenetic modification that regulates gene expression [QuickGO]. These complexes are conserved from yeast to humans and include well-characterized assemblies such as Hat1-Hat2, NuA3, NuA4, SAGA, and ATAC [3,6,7,8]. They play critical roles in chromatin remodeling, DNA repair, and transcriptional activation [2,5]. Understanding their structure and function is essential for deciphering epigenetic regulation in health and disease [1,4].
histone acetyltransferase complex At A Glance
| GO ID | GO:0000123 |
|---|---|
| GO term | histone acetyltransferase complex |
| Ontology | cellular_component |
| Synonym | histone acetylase complex |
| Major function | Histone acetylation and chromatin regulation |
| Subunits | Catalytic HATs and accessory proteins (e.g., Hat1, Hat2, NuA4, SAGA, ATAC) |
| Conservation | Conserved from yeast to humans |
| Associated processes | Transcription, DNA repair, cell cycle |
What Is GO:0000123?
GO:0000123, histone acetyltransferase complex, is a protein complex that possesses histone acetyltransferase activity, meaning it catalyzes the transfer of acetyl groups to lysine residues on histone proteins, thereby modulating chromatin structure and gene expression [QuickGO].
Why Is histone acetyltransferase complex Important in Cell Biology?
Histone acetyltransferase complexes are central to epigenetic regulation, controlling gene expression programs that influence development, differentiation, and disease [1,2,5]. Their dysfunction is implicated in cancer, neurodegeneration, and metabolic disorders, making them attractive therapeutic targets [1,4].
• Regulate chromatin accessibility and transcription [2,5].
• Involved in DNA damage repair and cell cycle progression [3,6].
• Mutations in HAT complex subunits are linked to cancer [1,4].
• Required for chlorophyll biosynthesis and photosynthesis in plants.
• Targets for small-molecule inhibitors in cancer therapy.
• Essential for histone deposition and nucleosome assembly.
• Modulate H3K14 acetylation and gene activation.
• Coordinate cytoplasmic and nuclear acetylation in Arabidopsis.
What Happens During histone acetyltransferase complex?
Histone substrate recognition
In simple terms: The complex first grabs onto histone proteins.
The Hat1-Hat2 complex interacts with histone H3-H4, with specific topography determining acetylation sites. NuA3 recognizes histone H3 tails to acetylate K14.
Catalytic acetylation
In simple terms: The complex adds acetyl groups to histones.
Acetyl-CoA is used by the catalytic subunit to transfer acetyl groups to lysine residues, neutralizing positive charge and loosening chromatin [3,6].
Chromatin remodeling and transcription
In simple terms: Acetylation opens DNA for reading.
Acetylation by SAGA and NuA4 promotes recruitment of transcription factors and RNA polymerase II, enhancing gene expression [2,5].
Cytoplasmic and nuclear coordination
In simple terms: The complex works in different cell compartments.
In Arabidopsis, the HAT complex coordinates cytoplasmic histone acetylation with nuclear chromatin accessibility.
Key Genes Involved in GO:0000123 histone acetyltransferase complex
Key genes encoding subunits of histone acetyltransferase complexes are listed below.
| Gene | Major Role | Research Relevance |
|---|---|---|
| HAT1 | Catalytic subunit of Hat1-Hat2 complex | Histone deposition and tumorigenesis [1,7] |
| HAT2 | Accessory subunit in Hat1-Hat2 | Histone H3-H4 interaction |
| GCN5 | Catalytic subunit of SAGA and ATAC | Transcription and development |
| PCAF | HAT in SAGA-like complexes | Cancer and differentiation |
| EP400 | Scaffold of NuA4 complex | Chromatin remodeling |
| TRRAP | Shared subunit of NuA4 and SAGA | Transcriptional coactivation [3,6] |
| EAF1 | NuA4 subunit | Histone acetylation and DNA repair |
| EAF3 | NuA4 subunit | Chromatin binding |
| EAF5 | NuA4 subunit | Complex assembly |
| EAF6 | NuA4 subunit | Structural integrity |
| EAF7 | NuA4 subunit | Histone acetylation |
| YAF9 | NuA4 subunit | Chromatin modification |
| ARP4 | NuA4 subunit | Nucleosome interaction |
| SWC4 | NuA4 subunit | Complex stability |
| TRA1 | NuA4 subunit | Transcriptional regulation |
| SGF29 | SAGA subunit | Histone acetylation |
| ADA2 | SAGA subunit | HAT module assembly |
| SPT7 | SAGA subunit | Transcription activation |
How Is histone acetyltransferase complex Regulated?
Histone acetyltransferase complexes are regulated by post-translational modifications of subunits, interaction with cofactors, and metabolic availability of acetyl-CoA [3,6]. In Arabidopsis, their activity is coordinated with cytoplasmic histone acetylation and nuclear chromatin accessibility.
histone acetyltransferase complex and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| HAT1 | Cancer | Knockout in cancer cell lines |
| EP400 | Developmental disorders | Point mutation in stem cells |
| GCN5 | Cancer | Overexpression in tumor models |
| TRRAP | Neurodegeneration | Knock-in in neurons |
| EAF1 | DNA repair defects | Knockout in fibroblasts |
Cancer
HAT1 promotes tumorigenesis through succinylation of histones and non-histones, and its overexpression is observed in various cancers. ATAC complex inhibitors show promise in cancer therapy.
Developmental disorders
Mutations in NuA4 subunits can lead to developmental defects due to impaired chromatin remodeling.
Metabolic diseases
Dysregulation of HAT complexes affects metabolic gene expression, contributing to obesity and diabetes.
From histone acetyltransferase complex-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Catalytic activity of HAT1 | Knockout cell line |
| Histone recognition by NuA3 | Point mutation in H3 |
| Complex assembly of NuA4 | Tagged knock-in |
| Role of SAGA in transcription | Overexpression of GCN5 |
| Cytoplasmic acetylation in plants | Arabidopsis knockout |
| Inhibitor specificity for ATAC | Knock-in reporter |
How to Study the histone acetyltransferase complex Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Cryo-EM | 3D structure | NuA4 and SAGA architecture [3,6] |
| Acetylation assay | Enzyme activity | HAT1 and NuA3 function [7,8] |
| ATAC-seq | Chromatin accessibility | Nuclear acetylation effects |
| Mass spectrometry | Protein interactions | Complex composition |
| ChIP-seq | Histone modification | H3K14ac mapping |
| RNA-seq | Gene expression | Transcriptional changes |
| CRISPR screen | Gene essentiality | HAT complex subunits |
Structural biology
Cryo-EM and X-ray crystallography reveal the architecture of NuA4 and SAGA complexes [3,6].
Histone acetylation assays
In vitro acetylation assays using recombinant histones and acetyl-CoA measure catalytic activity [7,8].
Chromatin accessibility assays
ATAC-seq and MNase-seq assess changes in chromatin openness upon HAT complex manipulation [2,5].
Proteomics
Mass spectrometry identifies subunit composition and post-translational modifications [1,4].
How CRISPR Can Be Used to Study GO:0000123 histone acetyltransferase complex
Knockout
CRISPR knockout of HAT1 or EP400 ablates complex function, revealing roles in tumorigenesis and development [1,3].
Point Mutation
Point mutations in catalytic residues or histone-binding domains dissect specific acetylation events [7,8].
Knock-in
Tagged knock-in of subunits enables live-cell imaging and proteomic analysis.
Overexpression
Overexpression of GCN5 or HAT1 models gain-of-function in cancer and metabolic diseases [1,4].
How EDITGENE Supports histone acetyltransferase complex Research
Researchers studying histone acetyltransferase complex-related genes often need to determine whether a candidate gene is causally involved in chromatin regulation and disease. EDITGENE provides tailored CRISPR services to address these questions.
Contact EDITGENE today to design your custom CRISPR model for histone acetyltransferase complex research.
Frequently Asked Questions About histone acetyltransferase complex
What is GO:0000123?
GO:0000123 is the Gene Ontology term for histone acetyltransferase complex, a protein complex that acetylates histones [QuickGO].
What genes are involved in histone acetyltransferase complex?
Key genes include HAT1, HAT2, GCN5, PCAF, EP400, TRRAP, and EAF1-7 [1,3,6,7].
What does histone acetyltransferase complex do?
It acetylates histone lysines, altering chromatin structure and regulating transcription [2,5].
How is histone acetyltransferase complex regulated?
It is regulated by subunit modifications, cofactors, and acetyl-CoA levels [3,6].
What diseases are linked to histone acetyltransferase complex?
Cancer, developmental disorders, and metabolic diseases [1,4].
What are the subunits of NuA4 complex?
NuA4 includes EP400, TRRAP, EAF1-7, YAF9, ARP4, SWC4, and TRA1.
How to study histone acetyltransferase complex with CRISPR?
Use knockout, point mutation, knock-in, and overexpression models [1,4,7].
What is the structure of SAGA complex?
SAGA contains a histone acetyltransferase module with GCN5, ADA2, and SGF29.
What is the role of HAT1 in cancer?
HAT1 promotes tumorigenesis via histone succinylation and is overexpressed in cancers.
What methods measure histone acetylation?
Acetylation assays, ChIP-seq, and mass spectrometry [7,8].
Conclusion
The histone acetyltransferase complex (GO:0000123) is a critical regulator of chromatin and gene expression, with diverse roles in development and disease. Understanding its components and mechanisms through CRISPR models will advance epigenetic research and therapeutic development [1,3,4].
References
- 1. Yang G et al.. 2021. Histone acetyltransferase 1 is a succinyltransferase for histones and non-histones and promotes tumorigenesis.. EMBO Rep 22(2):e50967 PMID: 33372411
- 2. Wu CJ et al.. 2024. Arabidopsis histone acetyltransferase complex coordinates cytoplasmic histone acetylation and nuclear chromatin accessibility.. Sci Adv 10(49):eadp1840 PMID: 39630902
- 3. Ji L et al.. 2022. Structure of the NuA4 histone acetyltransferase complex.. Proc Natl Acad Sci U S A 119(48):e2214313119 PMID: 36417436
- 4. Liu S et al.. 2026. Complex-specific inhibitors for interrogating ATAC histone acetyltransferase complex.. Nat Chem Biol 22(3):471-481 PMID: 41513852
- 5. Zhou JX et al.. 2022. The Arabidopsis NuA4 histone acetyltransferase complex is required for chlorophyll biosynthesis and photosynthesis.. J Integr Plant Biol 64(4):901-914 PMID: 35043580
- 6. Mattoo RUH et al.. 2025. Structure of the transcriptional co-activator SAGA complex, including the histone acetyltransferase module.. Mol Cell 85(23):4333-4346.e4 PMID: 41260211
- 7. Yue Y et al.. 2022. Topography of histone H3-H4 interaction with the Hat1-Hat2 acetyltransferase complex.. Genes Dev 36(7-8):408-413 PMID: 35393344
- 8. Shi W et al.. 2025. Mechanistic insights into histone recognition and H3K14 acetylation by the NuA3 histone acetyltransferase complex.. Nat Commun 17(1):342 PMID: 41318527
