GO:0043994 histone H3K23 acetyltransferase activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0043994 describes the enzymatic activity that transfers an acetyl group from acetyl-CoA to lysine 23 of histone H3, producing H3K23ac.
• The best-characterized enzymes carrying this activity are the MORF/KAT6B and KAT6A histone acetyltransferases, which act within MOZ/MORF and related complexes.
• H3K23 acetylation is often coupled to acylation of neighboring H3K14, and the two marks can influence each other on the same histone tail.
• Dysregulation of H3K23 acetyltransferase activity has been linked to cancer, neurodevelopmental disorders, and inflammatory responses after myocardial infarction.
• Small-molecule inhibitors of KAT6A/B can reduce H3K23 acetylation and show efficacy in KAT6A-high ER+ breast cancer models.
• CRISPR knockout, point-mutation, knock-in, and overexpression models are key tools for dissecting the causal role of H3K23 acetyltransferase activity in disease.
Description
Histone H3K23 acetyltransferase activity (GO:0043994) is a molecular function defined as the catalysis of the reaction acetyl-CoA + histone H3 L-lysine at position 23 = CoA + histone H3 N6-acetyl-L-lysine at position 23. In practical terms, it is the activity that places an acetyl mark on lysine 23 of histone H3, a modification known as H3K23ac. This mark is deposited by histone acetyltransferase enzymes and is recognized as part of the broader histone acetylation code that regulates chromatin accessibility and gene expression. The activity is best documented for the MORF (KAT6B) and KAT6A enzymes, which are subunits of multi-protein histone acetyltransferase complexes. Biochemical and structural studies have shown that MORF can acetylate H3K23 in a manner coupled to acylation at H3K14, revealing crosstalk between adjacent histone marks. KAT6A and KAT6B complexes also contain BRPF1, which contributes to substrate recognition and complex integrity, and mutations in these components are associated with neurodevelopmental disorders and cancer. For researchers, GO:0043994 matters because H3K23 acetylation is not merely a passive chromatin mark. It has been implicated in transcriptional control, developmental gene regulation, and disease processes including breast cancer, hepatocellular carcinoma, and post-infarction inflammation. Understanding which enzymes carry this activity, how it is regulated, and which genes it controls requires precise experimental models, including CRISPR-based knockouts, point mutants, and knock-ins.
histone H3K23 acetyltransferase activity At A Glance
| GO ID | GO:0043994 |
|---|---|
| GO term | histone H3K23 acetyltransferase activity |
| Ontology | molecular_function |
| Synonym | histone acetylase activity (H3-K23 specific); histone acetyltransferase activity (H3-K23 specific); histone H3-K23 acetyltransferase activity; histone lysine N-acetyltransferase activity (H3-K23 specific) |
| Major function | Catalyzes acetyl transfer from acetyl-CoA to histone H3 lysine 23, producing H3K23ac and CoA |
| Reaction | acetyl-CoA + histone H3 L-lysine (position 23) = CoA + histone H3 N6-acetyl-L-lysine (position 23) |
| Substrate | Histone H3, lysine 23; acetyl-CoA as acetyl donor |
| Representative enzymes | MORF/KAT6B, KAT6A, and associated HAT complexes |
| Cellular context | Nuclear chromatin; regulates transcription and chromatin state |
What Is GO:0043994?
GO:0043994, histone H3K23 acetyltransferase activity, is the catalytic activity that transfers an acetyl group from acetyl-CoA to the epsilon-amino group of lysine 23 on histone H3. The reaction yields CoA and histone H3 N6-acetyl-L-lysine at position 23. This activity is a molecular_function in the Gene Ontology and is synonymous with histone acetylase activity (H3-K23 specific), histone acetyltransferase activity (H3-K23 specific), histone H3-K23 acetyltransferase activity, and histone lysine N-acetyltransferase activity (H3-K23 specific). It is distinct from acetyltransferase activities that target other histone residues or non-histone substrates.
Why Is histone H3K23 acetyltransferase activity Important in Cell Biology?
Histone H3K23 acetyltransferase activity is important because it generates a chromatin mark that influences gene expression programs relevant to development, cancer, and inflammation. The activity is carried out by enzymes such as MORF/KAT6B and KAT6A, which are frequently altered in human disease. Pharmacological inhibition of KAT6A/B reduces H3K23 acetylation and has shown efficacy in KAT6A-high ER+ breast cancer models, demonstrating that this activity is a tractable therapeutic target. In addition, H3K23 acetylation can be coupled to acylation at H3K14, suggesting that it participates in a broader network of histone modifications that fine-tune chromatin function. Understanding GO:0043994 therefore helps researchers interpret how histone acetyltransferases shape disease-relevant transcriptional states.
• H3K23 acetylation is a chromatin mark deposited by histone acetyltransferases such as MORF/KAT6B and KAT6A.
• The activity is coupled to H3K14 acylation, revealing crosstalk between adjacent histone modifications.
• KAT6A/B inhibitors that reduce H3K23 acetylation show efficacy in KAT6A-high ER+ breast cancer models.
• KAT6A upregulates PI3K/AKT signaling through TRIM24 binding, linking H3K23-related acetylation to oncogenic pathways.
• Matrix stiffness-induced KAT6A promotes hepatocellular carcinoma progression by regulating SOX2 expression.
• BRPF1-KAT6 complexes are implicated in neurodevelopmental disorders and cancer through deficient histone H3 propionylation.
• Histone acetyltransferase 1 promotes post-infarction inflammatory responses via monocyte histone succinylation.
• H3K23 acetylation is part of the histone code that regulates chromatin accessibility and transcription.
• Drosophila studies of Enok (KAT6A homolog) and its partner Tctp provide genetic evidence for HAT complex function in chromatin binding.
• Plant HAF2 associates with PDC to control H3K14ac and H3K23ac in ethylene response, showing evolutionary conservation of the mark.
What Happens During histone H3K23 acetyltransferase activity?
Recognition of histone H3 substrate
In simple terms: The enzyme first finds and binds the histone H3 protein.
Histone H3K23 acetyltransferase activity requires the enzyme to recognize histone H3 as a substrate. In the MORF/KAT6B complex, structural and biochemical studies have shown that the enzyme engages the histone H3 tail and can acetylate H3K23 in a manner coupled to acylation at H3K14. The BRPF1 subunit within KAT6 complexes contributes to substrate recognition and complex integrity, and its dysfunction is linked to neurodevelopmental disorders and cancer.
Acetyl-CoA binding and acetyl transfer
In simple terms: The enzyme takes an acetyl group from acetyl-CoA and attaches it to lysine 23 of histone H3.
The catalytic step of GO:0043994 involves binding of the cofactor acetyl-CoA and transfer of its acetyl group to the epsilon-amino group of histone H3 lysine 23. This produces CoA and histone H3 N6-acetyl-L-lysine at position 23. The reaction is carried out by histone acetyltransferase enzymes such as MORF/KAT6B and KAT6A within multi-protein complexes.
Crosstalk with H3K14 acylation
In simple terms: The mark at position 23 is often connected to modifications at the nearby position 14.
H3K23 acetylation is coupled to H3K14 acylation, meaning that the two adjacent marks can influence each other on the same histone tail. In plants, the histone acetyltransferase HAF2 associates with PDC to control both H3K14ac and H3K23ac during ethylene response, further supporting coordinated regulation of these residues. This crosstalk suggests that H3K23 acetyltransferase activity operates within a combinatorial histone modification network rather than in isolation.
Chromatin and transcriptional consequences
In simple terms: Once the mark is placed, it can change how genes are turned on or off.
Deposition of H3K23ac by histone acetyltransferases contributes to chromatin states that regulate transcription. KAT6A upregulates PI3K/AKT signaling through TRIM24 binding, linking H3K23-related acetylation to oncogenic transcriptional programs. Matrix stiffness-induced upregulation of KAT6A promotes hepatocellular carcinoma progression by regulating SOX2 expression, showing that H3K23 acetyltransferase activity can feed into stemness-associated gene networks. In breast cancer, KAT6A/B inhibition reduces H3K23 acetylation and shows efficacy in KAT6A-high ER+ models.
Key Genes Involved in GO:0043994 histone H3K23 acetyltransferase activity
The following genes and proteins are experimentally linked to histone H3K23 acetyltransferase activity or its regulatory complexes.
| Gene | Major Role | Research Relevance |
|---|---|---|
| KAT6B (MORF) | Histone acetyltransferase that can acetylate H3K23 in a manner coupled to H3K14 acylation | Core enzyme for studying GO:0043994; structural and biochemical models |
| KAT6A (MOZ) | Histone acetyltransferase in KAT6 complexes; linked to PI3K/AKT signaling and SOX2 regulation | Oncogenic HAT; target for inhibitors in ER+ breast cancer |
| BRPF1 | Subunit of KAT6 complexes; contributes to substrate recognition and complex integrity | Mutations linked to neurodevelopmental disorders and cancer |
| TRIM24 | Binds KAT6A and mediates PI3K/AKT upregulation | Link between H3K23-related acetylation and oncogenic signaling |
| SOX2 | Transcription factor regulated downstream of KAT6A in hepatocellular carcinoma | Stemness and cancer progression model |
| HAF2 | Plant histone acetyltransferase associated with PDC; controls H3K14ac and H3K23ac | Evolutionary conservation of H3K23 acetylation |
| PDC | Associates with HAF2 to control H3K14ac and H3K23ac in ethylene response | Plant model for H3K23 acetylation regulation |
| Enok | Drosophila KAT6A homolog; chromatin binding inhibited by Tctp | Genetic model for HAT complex function |
| Tctp | Unique Ing5-binding partner; inhibits chromatin binding of Enok in Drosophila | Regulator of HAT complex chromatin association |
| Ing5 | Component of Drosophila HAT complex; binds Tctp | Complex assembly and chromatin regulation |
| HAT1 | Histone acetyltransferase 1; promotes post-infarction inflammatory response via monocyte histone succinylation | Inflammation and myocardial infarction model |
| KAT6A/B (as targets) | Enzymes whose inhibition reduces H3K23 acetylation | Drug discovery and therapeutic targeting |
| MOZ/MORF complex | Multi-protein HAT complex containing KAT6A/KAT6B | Biochemical reconstitution and structural studies |
| Histone H3 | Substrate for acetylation at lysine 23 | Core substrate for enzymatic assays |
| Acetyl-CoA | Acetyl donor for the reaction | Cofactor in enzymatic and metabolic studies |
| BRPF1-KAT6 complex | Complex implicated in neurodevelopmental disorders and cancer | Disease modeling and mutation studies |
| KAT6A-high ER+ breast cancer models | Tumor models sensitive to KAT6A/B inhibition | Preclinical efficacy testing |
| Monocyte histone succinylation pathway | Linked to HAT1 in post-infarction inflammation | Inflammatory disease research |
How Is histone H3K23 acetyltransferase activity Regulated?
Histone H3K23 acetyltransferase activity is regulated at multiple levels. The assembly and integrity of KAT6 complexes depend on subunits such as BRPF1, and mutations in these components can alter H3K23 acetylation and contribute to neurodevelopmental disorders and cancer. In Drosophila, the chromatin binding of Enok (a KAT6A homolog) is inhibited by Tctp, a unique Ing5-binding partner, providing a genetic mechanism for regulating HAT complex localization. In plants, HAF2 associates with PDC to control H3K14ac and H3K23ac during ethylene response, showing that environmental and hormonal signals can influence H3K23 acetylation. Additionally, HAT1 promotes post-infarction inflammatory responses through regulation of monocyte histone succinylation, indicating that metabolic and inflammatory cues can intersect with histone acetylation pathways. Pharmacological inhibition of KAT6A/B reduces H3K23 acetylation, demonstrating that the activity is druggable and can be modulated exogenously.
histone H3K23 acetyltransferase activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| KAT6A | ER+ breast cancer; hepatocellular carcinoma; PI3K/AKT signaling | KAT6A-high ER+ breast cancer xenografts; HCC cell lines with matrix stiffness |
| KAT6B (MORF) | Neurodevelopmental disorders; cancer | KO and point-mutation cell models; biochemical HAT assays |
| BRPF1 | Neurodevelopmental disorders and cancer | BRPF1 mutant knock-in models; KAT6 complex reconstitution |
| HAT1 | Post-infarction inflammatory response | Monocyte-specific KO; myocardial infarction mouse models |
| HAF2 | Ethylene response in plants | Plant HAF2 mutants; PDC interaction studies |
Cancer
H3K23 acetyltransferase activity has been linked to multiple cancers. KAT6A upregulates PI3K/AKT signaling through TRIM24 binding, promoting oncogenic pathways. Matrix stiffness-induced upregulation of KAT6A promotes hepatocellular carcinoma progression by regulating SOX2 expression. In breast cancer, a highly potent, selective, orally bioavailable inhibitor of KAT6A/B reduces H3K23 acetylation and shows efficacy against KAT6A-high ER+ breast cancer. These findings suggest that H3K23 acetylation contributes to tumorigenic transcriptional programs.
Neurodevelopmental disorders
Deficient histone H3 propionylation by BRPF1-KAT6 complexes has been implicated in neurodevelopmental disorders and cancer. Because BRPF1 is a subunit of KAT6 complexes that carry H3K23 acetyltransferase activity, mutations affecting these complexes may disrupt normal chromatin regulation during development.
Inflammation and cardiovascular disease
Histone acetyltransferase 1 promotes post-infarction inflammatory response by regulating monocyte histone succinylation. This links histone acetylation-related enzymes to inflammatory processes after myocardial infarction, although the specific relationship to H3K23 acetylation requires further study.
Plant development and ethylene response
In plants, HAF2 associates with PDC to control H3K14ac and H3K23ac in ethylene response. This demonstrates that H3K23 acetylation is conserved beyond animals and plays a role in hormone-regulated developmental processes.
From histone H3K23 acetyltransferase activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of KAT6A/B reduce H3K23 acetylation and tumor growth? | CRISPR knockout of KAT6A/B in ER+ breast cancer cell lines and xenografts |
| How do disease-associated mutations in BRPF1 affect KAT6 complex function? | Point-mutation knock-in of BRPF1 variants in cell models |
| Can H3K23 acetylation be monitored in live cells? | Tagged knock-in of histone H3 or HAT enzymes with fluorescent or affinity tags |
| What transcriptional programs depend on H3K23 acetyltransferase activity? | Overexpression and knockout of KAT6A followed by RNA-seq |
| Is H3K23 acetylation coupled to H3K14 acylation? | Point-mutation of H3K14 and H3K23 residues; biochemical HAT assays |
| Does HAT1 regulate inflammatory gene expression after myocardial infarction? | Monocyte-specific knockout and overexpression models |
How to Study the histone H3K23 acetyltransferase activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| In vitro HAT assay | Enzymatic transfer of acetyl to H3K23 | Confirming GO:0043994 activity of candidate enzymes |
| ChIP-seq | Genomic localization of H3K23ac | Mapping chromatin marks and target genes |
| RNA-seq | Transcriptional changes after perturbation | Identifying gene networks regulated by H3K23 acetylation |
| Mass spectrometry | Quantification of histone modifications | Detecting H3K23ac and crosstalk with H3K14ac |
| CRISPR knockout | Loss of gene function | Testing causal role of KAT6A/B in cancer models |
| CRISPR point mutation | Specific amino acid changes | Modeling disease-associated mutations in BRPF1 |
| CRISPR knock-in | Tagged or mutant alleles | Live-cell imaging and affinity purification |
| Overexpression | Gain of function | Studying KAT6A-driven oncogenic pathways |
Biochemical HAT assays
In vitro histone acetyltransferase assays using recombinant enzymes and histone substrates can directly measure H3K23 acetylation. These assays use acetyl-CoA and detect the production of H3K23ac by immunoblotting or mass spectrometry. They are essential for confirming that a candidate enzyme carries GO:0043994 activity.
Chromatin immunoprecipitation and sequencing
ChIP-seq with anti-H3K23ac antibodies can map the genomic distribution of this mark and correlate it with transcriptional activity. Combining ChIP-seq with RNA-seq after KAT6A/B inhibition or knockout helps identify genes regulated by H3K23 acetylation.
CRISPR-based genetic models
CRISPR knockout, point-mutation knock-in, and overexpression models allow causal testing of H3K23 acetyltransferase activity. For example, KAT6A/B knockout reduces H3K23 acetylation and affects breast cancer cell growth, while BRPF1 mutations can be introduced to study neurodevelopmental disorders.
Proteomics and mass spectrometry
Mass spectrometry-based proteomics can quantify histone modifications, including H3K23ac, and identify crosstalk with other marks such as H3K14ac. This approach is useful for unbiased profiling of histone modification changes after genetic or pharmacological perturbation.
How CRISPR Can Be Used to Study GO:0043994 histone H3K23 acetyltransferase activity
Knockout
CRISPR knockout of KAT6A or KAT6B eliminates the enzymes responsible for H3K23 acetyltransferase activity, allowing researchers to measure loss of H3K23ac and downstream transcriptional effects. For example, KAT6A/B inhibition or knockout reduces H3K23 acetylation and shows efficacy in KAT6A-high ER+ breast cancer models. Knockout models are also used to study BRPF1-KAT6 complex function in neurodevelopmental disorders.
Point Mutation
CRISPR point mutation can introduce specific amino acid substitutions in HAT enzymes or histone H3 to dissect catalytic residues or crosstalk sites. For instance, mutating H3K14 or H3K23 can test whether acetylation at one residue depends on the other. Point mutations in BRPF1 can model disease-associated variants that impair KAT6 complex function.
Knock-in
CRISPR knock-in of tagged histone H3 or HAT enzymes enables live-cell imaging, chromatin immunoprecipitation, and affinity purification of complexes. Tagged knock-in models help track H3K23 acetylation dynamics and identify interacting proteins in native chromatin contexts.
Overexpression
CRISPR-mediated overexpression or cDNA overexpression of KAT6A, KAT6B, or BRPF1 can drive gain-of-function phenotypes. Overexpression of KAT6A upregulates PI3K/AKT signaling through TRIM24 binding and promotes hepatocellular carcinoma progression via SOX2, providing models to study oncogenic mechanisms linked to H3K23 acetylation.
How EDITGENE Supports histone H3K23 acetyltransferase activity Research
Researchers studying histone H3K23 acetyltransferase activity-related genes often need to determine whether a candidate gene is causally involved in a specific disease or chromatin phenotype. This requires precise genetic models that can knockout, mutate, tag, or overexpress the gene of interest in relevant cell types. EDITGENE provides a comprehensive suite of CRISPR services tailored to these needs, enabling rigorous functional studies of H3K23 acetyltransferase activity and its regulatory network.
Contact EDITGENE today to design your custom CRISPR model for histone H3K23 acetyltransferase activity research.
Frequently Asked Questions About histone H3K23 acetyltransferase activity
What is histone H3K23 acetyltransferase activity?
It is the enzymatic activity defined by GO:0043994 that transfers an acetyl group from acetyl-CoA to lysine 23 of histone H3, producing H3K23ac and CoA.
What genes are involved in histone H3K23 acetyltransferase activity?
The best-characterized genes are KAT6B (MORF) and KAT6A, which encode histone acetyltransferases that can acetylate H3K23. BRPF1, TRIM24, and SOX2 are also linked to these pathways.
Which enzymes carry H3K23 acetyltransferase activity?
MORF/KAT6B and KAT6A are the primary enzymes reported to carry this activity, often within multi-protein complexes containing BRPF1.
How is H3K23 acetylation coupled to H3K14 acylation?
Biochemical studies show that MORF can acetylate H3K23 in a manner coupled to acylation at H3K14, indicating crosstalk between adjacent histone marks.
What diseases are associated with H3K23 acetyltransferase activity?
It has been linked to ER+ breast cancer, hepatocellular carcinoma, neurodevelopmental disorders, and post-infarction inflammation.
Can H3K23 acetyltransferase activity be inhibited pharmacologically?
Yes, a highly potent, selective, orally bioavailable inhibitor of KAT6A/B reduces H3K23 acetylation and shows efficacy in KAT6A-high ER+ breast cancer models.
How can I study H3K23 acetylation in the lab?
Common methods include in vitro HAT assays, ChIP-seq, RNA-seq, mass spectrometry, and CRISPR-based knockout, point-mutation, knock-in, or overexpression models.
Is H3K23 acetylation conserved in plants?
Yes, the plant histone acetyltransferase HAF2 associates with PDC to control H3K14ac and H3K23ac during ethylene response.
What is the role of KAT6A in cancer?
KAT6A upregulates PI3K/AKT signaling through TRIM24 binding and promotes hepatocellular carcinoma progression by regulating SOX2 expression.
What CRISPR models are available for H3K23 acetyltransferase research?
EDITGENE offers knockout, point-mutation, knock-in, tagged knock-in, and overexpression cell models, as well as CRISPR library screening and bioinformatics services.
Conclusion
Histone H3K23 acetyltransferase activity (GO:0043994) is a molecular function that deposits the H3K23ac mark, a modification with emerging roles in cancer, neurodevelopment, and inflammation. The enzymes MORF/KAT6B and KAT6A, along with their complex partners such as BRPF1, are central to this activity, and their dysregulation contributes to disease. Pharmacological inhibition of KAT6A/B reduces H3K23 acetylation and shows therapeutic potential in breast cancer, underscoring the importance of this activity as a drug target. Continued research using CRISPR knockout, point-mutation, knock-in, and overexpression models will clarify how H3K23 acetylation is regulated and which gene networks it controls. EDITGENE provides the tools and services needed to build these models and to analyze the resulting chromatin and transcriptional data, accelerating discoveries in this field.
References
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- 2. Guo Y et al.. 2025. Histone acetyltransferase 1 promotes postinfarction inflammatory response by regulation of monocyte histone succinylation.. Nat Commun 16(1):11718 PMID: 41315268
- 3. Klein BJ et al.. 2019. Histone H3K23-specific acetylation by MORF is coupled to H3K14 acylation.. Nat Commun 10(1):4724 PMID: 31624313
- 4. Chen CY et al.. 2024. Histone acetyltransferase HAF2 associates with PDC to control H3K14ac and H3K23ac in ethylene response.. bioRxiv PMID: 38260516
- 5. Yan K et al.. 2020. Deficient histone H3 propionylation by BRPF1-KAT6 complexes in neurodevelopmental disorders and cancer.. Sci Adv 6(4):eaax0021 PMID: 32010779
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