GO:0016407 acetyltransferase activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0016407 acetyltransferase activity describes the catalysis of acetyl group transfer to an acceptor molecule, a fundamental molecular function in gene regulation and metabolism.
• Acetyltransferase enzymes such as CBP, P/CAF, and N-acetylglutamate synthase use acetyl-CoA as a cofactor to modify histones, transcription factors, and small molecules.
• Dysregulated acetyltransferase activity is linked to cancer, developmental disorders, and metabolic diseases, making it a key therapeutic target.
• CRISPR-based epigenome editing has been used to directly recruit acetyltransferase domains to specific loci, activating endogenous genes.
• Studying acetyltransferase activity requires a combination of biochemical assays, CRISPR knockout/knock-in models, and high-throughput sequencing methods.
• EDITGENE provides comprehensive CRISPR services including knockout, point mutation, knock-in, overexpression, and library screening to accelerate acetyltransferase research.
Description
Acetyltransferase activity (GO:0016407) is a molecular function defined as the catalysis of the transfer of an acetyl group to an acceptor molecule. This activity is central to numerous biological processes, including transcriptional regulation, metabolism, and signal transduction. The acetyl group donor is typically acetyl-coenzyme A (acetyl-CoA), and the acceptor can be a protein, a small molecule, or a lipid. Acetyltransferases are encoded by a large family of genes, and their dysfunction has been implicated in a wide range of human diseases, from cancer to inborn errors of metabolism. Researchers study acetyltransferase activity to understand how cells control gene expression, respond to environmental cues, and maintain metabolic homeostasis. For example, the acetyltransferase activity of CBP (CREB-binding protein) is required for transcription of specific genes during development. Similarly, BRCA2-associated acetyltransferase activity, when bound to P/CAF, suggests a role in DNA repair and tumor suppression. The broad impact of this activity makes it a prime target for therapeutic intervention and a focus of intense biomedical research. This article provides a comprehensive overview of acetyltransferase activity, covering its definition, mechanism, key genes, disease associations, and the research methods used to study it. We also highlight how CRISPR-based tools and EDITGENE services can accelerate discoveries in this field.
acetyltransferase activity At A Glance
| GO ID | GO:0016407 |
|---|---|
| GO term | acetyltransferase activity |
| Ontology | molecular_function |
| Synonym | acetylase activity |
| Major function | Transfer of an acetyl group to an acceptor molecule |
| Cofactor | Acetyl-CoA (common donor) |
| Substrates | Proteins (e.g., histones), small molecules, lipids |
| Related processes | Transcription regulation, metabolism, signal transduction |
What Is GO:0016407?
According to the Gene Ontology, acetyltransferase activity (GO:0016407) is the catalysis of the transfer of an acetyl group to an acceptor molecule. This activity is synonymous with acetylase activity. It is a molecular function that enables the covalent attachment of an acetyl moiety, typically derived from acetyl-CoA, to a substrate. This modification can alter the substrate's properties, such as its charge, stability, or interaction with other molecules, thereby regulating diverse cellular processes.
Why Is acetyltransferase activity Important in Cell Biology?
Acetyltransferase activity is essential for a myriad of cellular processes, from epigenetic regulation of gene expression to metabolic control. Its dysregulation is associated with cancer, developmental disorders, and metabolic diseases, making it a critical area of study for understanding disease mechanisms and developing targeted therapies.
• Regulates gene expression by acetylating histones and transcription factors.
• Modulates protein function, stability, and interactions.
• Involved in metabolic pathways, such as the urea cycle via N-acetylglutamate synthase.
• Plays a role in DNA repair and genome stability through BRCA2-associated activity.
• Required for developmental signaling pathways, e.g., Wingless activation in Drosophila.
• Target for cancer therapy due to its role in oncogenesis.
• Can be engineered for epigenome editing to activate endogenous genes.
• Subject to regulation by cofactors and post-translational modifications.
• Involved in inflammatory responses, e.g., lysoPAF acetyltransferase.
• Potential biomarker for metabolic and nutritional studies.
Molecular Mechanism of acetyltransferase activity
Substrate Binding and Acetyl-CoA Cofactor
In simple terms: The enzyme grabs an acetyl group from acetyl-CoA and holds it ready to attach to a target molecule.
Acetyltransferases typically bind acetyl-coenzyme A (acetyl-CoA) as a cofactor, positioning the acetyl group for transfer to an acceptor substrate. The enzyme's active site accommodates both the donor and acceptor, facilitating the catalytic reaction. For example, CBP utilizes acetyl-CoA to acetylate histone lysine residues, neutralizing their positive charge and altering chromatin structure.
Catalytic Transfer of the Acetyl Group
In simple terms: The enzyme transfers the acetyl group onto the target molecule, changing its properties.
The catalytic mechanism involves the nucleophilic attack of the acceptor's functional group (e.g., a lysine ε-amino group) on the acetyl-CoA thioester, resulting in the covalent attachment of the acetyl group and release of coenzyme A. This modification can alter the substrate's activity, localization, or interactions. The acetyltransferase activity of CBP is required for H4 acetylation and Wingless activation in Drosophila.
Regulation by Protein-Protein Interactions
In simple terms: Other proteins can turn the enzyme on or off by binding to it.
Acetyltransferase activity is often regulated through interactions with partner proteins. For instance, BRCA2 associates with acetyltransferase activity when bound to P/CAF, suggesting that complex formation modulates substrate specificity or catalytic efficiency. Similarly, transcriptional coactivator complexes recruit acetyltransferases to specific promoters to activate gene expression.
Subcellular Localization and Targeting
In simple terms: The enzyme goes to specific places in the cell to do its job.
Acetyltransferases are targeted to distinct subcellular compartments or chromatin regions to acetylate specific substrates. For example, nuclear acetyltransferases like CBP and P/CAF are recruited to promoters and enhancers, while mitochondrial acetyltransferases modify metabolic enzymes. This spatial regulation ensures precise control of acetyltransferase activity.
Reversibility and Deacetylation
In simple terms: The acetyl mark can be removed by other enzymes, making the process reversible.
Acetylation is a reversible modification; deacetylases (HDACs and sirtuins) remove acetyl groups, counterbalancing acetyltransferase activity. This dynamic interplay regulates gene expression and metabolic states. The balance between acetylation and deacetylation is crucial for cellular homeostasis.
Key Genes Involved in GO:0016407 acetyltransferase activity
The following genes encode proteins with acetyltransferase activity or are closely associated with this function, as supported by published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| CBP (CREBBP) | Histone acetyltransferase, transcriptional coactivator | Required for transcription, development; mutated in Rubinstein-Taybi syndrome |
| P/CAF (KAT2B) | Histone acetyltransferase, interacts with BRCA2 | Role in DNA repair, cancer |
| N-acetylglutamate synthase (NAGS) | Catalyzes N-acetylglutamate synthesis | Urea cycle regulation, hyperammonemia |
| LysoPAF acetyltransferase | Acetylates lysoPAF to PAF | Inflammation, allergy |
| BRCA2 | Associates with acetyltransferase activity | DNA repair, cancer susceptibility |
| GCN5 (KAT2A) | Histone acetyltransferase | Transcription regulation, development |
| TIP60 (KAT5) | Histone acetyltransferase | DNA damage response, cancer |
| MOZ (KAT6A) | Histone acetyltransferase | Leukemia, development |
| MORF (KAT6B) | Histone acetyltransferase | Development, cancer |
| p300 (EP300) | Histone acetyltransferase | Transcription, cancer |
| HAT1 | Histone acetyltransferase | Chromatin assembly |
| ELP3 | Histone acetyltransferase | Transcription elongation |
| SAS2 (KAT8) | Histone acetyltransferase | Dosage compensation, cancer |
| SAS3 (KAT6) | Histone acetyltransferase | Transcription |
| NAT1 | N-acetyltransferase | Drug metabolism, cancer |
| NAT2 | N-acetyltransferase | Drug metabolism, cancer |
| ARD1 (NAA10) | N-alpha-acetyltransferase | Protein stability, cancer |
How Is acetyltransferase activity Regulated?
Acetyltransferase activity is regulated at multiple levels, including cofactor availability (acetyl-CoA), post-translational modifications, and protein-protein interactions. For example, the acetyltransferase activity of CBP is required for Wingless activation and H4 acetylation in Drosophila, linking it to developmental signaling. Additionally, BRCA2 binding to P/CAF modulates acetyltransferase activity, implicating it in DNA repair pathways. Metabolic status can influence acetyl-CoA levels, thereby affecting acetyltransferase activity.
acetyltransferase activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| CBP (CREBBP) | Rubinstein-Taybi syndrome, cancer | Knockout mice, patient-derived iPSCs |
| BRCA2 | Breast/ovarian cancer, DNA repair | Knockout cell lines, xenografts |
| NAGS | Hyperammonemia, urea cycle disorder | Knockout mice, liver-specific KO |
| LysoPAF acetyltransferase | Inflammation, allergy | Knockout mice, inflammatory models |
| P/CAF (KAT2B) | Cancer, DNA repair | Knockout cell lines, CRISPR screens |
Cancer
Dysregulated acetyltransferase activity is frequently observed in cancer. For instance, BRCA2-associated acetyltransferase activity when bound to P/CAF suggests a role in tumor suppression, and mutations in acetyltransferases like CBP and p300 are linked to various malignancies. Targeting acetyltransferases is a promising therapeutic strategy.
Developmental Disorders
Mutations in genes encoding acetyltransferases, such as CBP, cause Rubinstein-Taybi syndrome, characterized by developmental delay and intellectual disability. The acetyltransferase activity of CBP is essential for proper development, as shown in Drosophila models.
Metabolic Diseases
N-acetylglutamate synthase deficiency leads to hyperammonemia due to impaired urea cycle activation. This highlights the critical role of acetyltransferase activity in metabolic pathways. Additionally, nutritional interventions can affect desaturase and elongase activities, though direct links to acetyltransferases require further study.
Inflammatory Diseases
LysoPAF acetyltransferase activity is involved in the synthesis of platelet-activating factor (PAF), a potent mediator of inflammation. Inhibition of this activity by flavonoids suggests a potential anti-inflammatory strategy.
From acetyltransferase activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of acetyltransferase X affect gene expression? | CRISPR knockout cell line + RNA-seq |
| Does a point mutation in the catalytic domain alter activity? | CRISPR point mutation knock-in |
| Can a tagged acetyltransferase be used for ChIP-seq? | CRISPR knock-in of epitope tag |
| Does overexpression of acetyltransferase Y drive proliferation? | CRISPR overexpression (CRISPRa) or lentiviral overexpression |
| Which substrates are acetylated by enzyme Z? | Knockout + acetyl-proteomics |
| Can acetyltransferase activity be rewired to a new locus? | CRISPR-dCas9-p300 epigenome editing |
How to Study the acetyltransferase activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| In vitro acetyltransferase assay | Enzymatic activity | Kinetics, inhibitor screening |
| Acetyl-proteomics | Global acetylation sites | Substrate identification |
| ChIP-seq | Genomic binding of acetyltransferases | Target gene identification |
| RNA-seq | Transcriptional changes | Functional impact of KO/overexpression |
| CRISPR screen | Essentiality of acetyltransferases | Cancer dependency mapping |
| Epigenome editing | Targeted acetylation | Gene activation |
| Western blot | Protein acetylation levels | Validation of specific modifications |
| Immunofluorescence | Subcellular localization | Colocalization studies |
Biochemical Acetyltransferase Assays
In vitro assays using recombinant enzymes and acetyl-CoA measure the transfer of acetyl groups to peptide or protein substrates. These assays are fundamental for kinetic characterization and inhibitor screening.
CRISPR-Based Epigenome Editing
Fusion of catalytically dead Cas9 (dCas9) to acetyltransferase domains (e.g., p300) enables targeted acetylation of histones at specific loci, activating endogenous genes. This approach has been used to activate genes from promoters and enhancers.
Acetyl-Proteomics
Mass spectrometry-based acetyl-proteomics identifies acetylated proteins and sites, providing a global view of acetyltransferase substrates. Comparing wild-type and knockout cells reveals specific targets.
Chromatin Immunoprecipitation (ChIP)
ChIP with antibodies against acetylated histones or tagged acetyltransferases maps their genomic binding sites, linking activity to transcriptional regulation.
How CRISPR Can Be Used to Study GO:0016407 acetyltransferase activity
Knockout
CRISPR knockout of acetyltransferase genes (e.g., CBP, P/CAF) enables loss-of-function studies to determine their role in gene expression, proliferation, and disease. Knockout cell lines are valuable for identifying substrates and pathways.
Point Mutation
Introducing point mutations in the catalytic domain of acetyltransferases (e.g., CBP) can abolish enzymatic activity without affecting protein levels, allowing precise dissection of catalytic vs. scaffolding functions.
Knock-in
Knock-in of epitope tags (e.g., FLAG, HA) or fluorescent proteins facilitates purification, imaging, and ChIP-seq of endogenous acetyltransferases, providing insights into their localization and interactions.
Overexpression
CRISPR activation (CRISPRa) or lentiviral overexpression of acetyltransferases can model gain-of-function states, such as those observed in cancer, and test whether increased activity drives oncogenic phenotypes.
How EDITGENE Supports acetyltransferase activity Research
Researchers studying acetyltransferase activity-related genes often need to determine whether a candidate gene is causally involved in a specific biological process or disease. EDITGENE provides a comprehensive suite of CRISPR services to generate precisely engineered cell models, enabling rigorous functional studies.
Contact EDITGENE today to design your custom CRISPR model for acetyltransferase activity research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KAT2B Knockout HEK293 Cell Line | EDJ-KQ429 | Human | 8850 | Details Get a Quote |
| CREBBP Knockout HEK293 Cell Line | EDJ-KQ454 | Human | 1387 | Details Get a Quote |
| EP300 Knockout HEK293 Cell Line | EDJ-KQ460 | Human | 2033 | Details Get a Quote |
| SPHK1 Knockout HEK293 Cell Line | EDJ-KQ1066 | Human | 8877 | Details Get a Quote |
| KAT6A Knockout HEK293 Cell Line | EDJ-KQ1108 | Human | 7994 | Details Get a Quote |
| NAT1 Knockout HEK293 Cell Line | EDJ-KQ2341 | Human | 9 | Details Get a Quote |
| NAT2 Knockout HEK293 Cell Line | EDJ-KQ2435 | Human | 10 | Details Get a Quote |
| MOGAT2 Knockout HEK293 Cell Line | EDJ-KQ2657 | Human | 80168 | Details Get a Quote |
| DLAT Knockout HEK293 Cell Line | EDJ-KQ3308 | Human | 1737 | Details Get a Quote |
| ESCO1 Knockout HEK293 Cell Line | EDJ-KQ7471 | Human | 114799 | Details Get a Quote |
| ATAT1 Knockout HEK293 Cell Line | EDJ-KQ12055 | Human | 79969 | Details Get a Quote |
| ESCO2 Knockout HEK293 Cell Line | EDJ-KQ13327 | Human | 157570 | Details Get a Quote |
| NAA16 Knockout HEK293 Cell Line | EDJ-KQ14355 | Human | 79612 | Details Get a Quote |
| KAT2B Knockout HCT 116 Cell Line | EDJ-KQ17999 | Human | 8850 | Details Get a Quote |
| CREBBP Knockout A-549 Cell Line | EDJ-KQ18005 | Human | 1387 | Details Get a Quote |
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Frequently Asked Questions About acetyltransferase activity
What is acetyltransferase activity?
Acetyltransferase activity (GO:0016407) is the catalysis of the transfer of an acetyl group to an acceptor molecule, typically using acetyl-CoA as a donor.
What genes are involved in acetyltransferase activity?
Key genes include CBP (CREBBP), P/CAF (KAT2B), NAGS, BRCA2, GCN5, TIP60, and many others that encode enzymes with acetyltransferase activity.
How is acetyltransferase activity regulated?
It is regulated by acetyl-CoA availability, protein-protein interactions, post-translational modifications, and subcellular localization.
What diseases are associated with acetyltransferase dysfunction?
Cancer, Rubinstein-Taybi syndrome, hyperammonemia, and inflammatory diseases are linked to altered acetyltransferase activity.
How can I study acetyltransferase activity in the lab?
Common methods include in vitro enzymatic assays, acetyl-proteomics, ChIP-seq, and CRISPR-based knockout or knock-in models.
What is the role of CBP acetyltransferase activity?
CBP acetyltransferase activity is required for transcription, histone acetylation, and developmental signaling, as shown in Drosophila and mammalian cells.
Can CRISPR be used to edit acetyltransferase genes?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression are widely used to study acetyltransferase function.
What is the connection between BRCA2 and acetyltransferase activity?
BRCA2 associates with acetyltransferase activity when bound to P/CAF, suggesting a role in DNA repair and tumor suppression.
What is N-acetylglutamate synthase?
N-acetylglutamate synthase is a mammalian enzyme with acetyltransferase activity that catalyzes the synthesis of N-acetylglutamate, an essential activator of the urea cycle.
How does lysoPAF acetyltransferase relate to inflammation?
LysoPAF acetyltransferase acetylates lysoPAF to form platelet-activating factor (PAF), a mediator of inflammation; its inhibition by flavonoids may reduce inflammation.
Conclusion
Acetyltransferase activity (GO:0016407) is a fundamental molecular function that regulates gene expression, metabolism, and development through the transfer of acetyl groups to diverse substrates. Its dysregulation contributes to cancer, developmental disorders, and metabolic diseases, making it a critical target for research and therapeutic development. Advances in CRISPR technology and biochemical assays continue to unravel the complexities of acetyltransferases, offering new opportunities for drug discovery. EDITGENE's comprehensive CRISPR services empower researchers to dissect the roles of acetyltransferases with precision and efficiency.
References
- 1. Hilton IB et al.. 2015. Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers.. Nat Biotechnol 33(5):510-7 PMID: 25849900
- 2. Martinez-Balbás MA et al.. 1998. The acetyltransferase activity of CBP stimulates transcription.. EMBO J 17(10):2886-93 PMID: 9582282
- 3. Venäläinen TM et al.. 2016. Effect of a 2-y dietary and physical activity intervention on plasma fatty acid composition and estimated desaturase and elongase activities in children: the Physical Activity and Nutrition in Children Study.. Am J Clin Nutr 104(4):964-972 PMID: 27581473
- 4. Yanoshita R et al.. 1996. Inhibition of lysoPAF acetyltransferase activity by flavonoids.. Inflamm Res 45(11):546-9 PMID: 8951505
- 5. Näär AM et al.. 2001. Transcriptional coactivator complexes.. Annu Rev Biochem 70:475-501 PMID: 11395415
- 6. Morizono H et al.. 2004. Mammalian N-acetylglutamate synthase.. Mol Genet Metab 81 Suppl 1(Suppl 1):S4-11 PMID: 15050968
- 7. Fuks F et al.. 1998. BRCA2 associates with acetyltransferase activity when bound to P/CAF.. Oncogene 17(19):2531-4 PMID: 9824164
- 8. Ludlam WH et al.. 2002. The acetyltransferase activity of CBP is required for wingless activation and H4 acetylation in Drosophila melanogaster.. Mol Cell Biol 22(11):3832-41 PMID: 11997517
