GO:0036408 histone H3K14 acetyltransferase activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0036408 describes the enzymatic activity that transfers an acetyl group from acetyl-CoA to lysine 14 of histone H3, producing H3K14ac.
• H3K14 acetylation is a chromatin mark linked to transcriptional activation and is implicated in cancer and other diseases.
• The principal enzymes carrying H3K14 acetyltransferase activity include KAT7 (MYST2/HBO1) and other MYST-family HATs such as HAF2 in plants.
• KAT7/HBO1 is a versatile acyltransferase that deposits H3K14ac and other acyl marks at promoters, influencing gene expression programs.
• Dysregulation of H3K14 acetylation, including impaired KAT7-dependent H3K14ac during zinc deficiency, has pathophysiological consequences.
• CRISPR-based knockout, point-mutation, knock-in, and overexpression models enable causal dissection of H3K14 acetyltransferase activity in disease and development.
Description
Histone H3 lysine 14 acetylation (H3K14ac) is a well-characterized chromatin modification that serves as a hallmark of active transcription and is dynamically regulated by histone acetyltransferases (HATs) and deacetylases. The Gene Ontology (GO) term GO:0036408, histone H3K14 acetyltransferase activity, precisely defines the enzymatic function responsible for depositing this mark: the acetyl-CoA-dependent acetylation of histone H3 at lysine 14. This activity is carried out by several HAT enzymes, most notably members of the MYST family such as KAT7 (also known as MYST2 or HBO1), which has emerged as a critical regulator of promoter histone acetylation and gene expression. Understanding GO:0036408 is essential for researchers studying chromatin biology, transcriptional regulation, and the epigenetic mechanisms underlying diseases such as cancer. The importance of H3K14 acetyltransferase activity extends beyond basic chromatin regulation. Recent studies have linked H3K14ac to colorectal cancer progression, where targeting KAT7 inhibits tumor growth, highlighting the therapeutic potential of modulating this activity. In addition, environmental factors such as zinc deficiency can impair KAT7-dependent H3K14 acetylation, leading to pathophysiological outcomes. In plants, HAF2, a homolog of human KAT7, associates with the PDC complex to control H3K14ac and H3K23ac during ethylene responses, demonstrating evolutionary conservation of this activity. These findings underscore the broad biological and clinical relevance of GO:0036408. This article provides a research-grade overview of GO:0036408, covering its definition, molecular mechanism, key genes, disease associations, and experimental models. By integrating authoritative GO annotations with verified PubMed literature, we aim to equip researchers with a comprehensive resource for studying histone H3K14 acetyltransferase activity and its role in health and disease.
histone H3K14 acetyltransferase activity At A Glance
| GO ID | GO:0036408 |
|---|---|
| GO term | histone H3K14 acetyltransferase activity |
| Ontology | molecular_function |
| Synonym | histone acetylase activity (H3-K14 specific); histone acetyltransferase activity (H3-K14 specific); histone H3-K14 acetyltransferase activity; histone lysine N-acetyltransferase activity (H3-K14 specific) |
| Major function | Catalyzes the acetylation of histone H3 at lysine 14 using acetyl-CoA as the acetyl donor. |
| Reaction | acetyl-CoA + histone H3 L-lysine (position 14) = CoA + histone H3 N6-acetyl-L-lysine (position 14) |
| Substrate | Histone H3 (lysine 14) and acetyl-CoA |
| Product | CoA and histone H3 N6-acetyl-L-lysine (position 14) (H3K14ac) |
| Cofactor | Acetyl-CoA serves as the acetyl group donor. |
| Localization | Nucleus, associated with chromatin at promoters and enhancers. |
What Is GO:0036408?
GO:0036408, histone H3K14 acetyltransferase activity, is a molecular function defined as the catalysis of the reaction: acetyl-CoA + histone H3 L-lysine (position 14) = CoA + histone H3 N6-acetyl-L-lysine (position 14). In other words, it is the enzyme activity that transfers an acetyl group from acetyl-CoA to the epsilon-amino group of lysine 14 on histone H3, resulting in the post-translational modification H3K14ac. This activity is specific to histone H3 at position 14 and is distinct from other histone acetyltransferase activities that target different lysine residues or histones.
Why Is histone H3K14 acetyltransferase activity Important in Cell Biology?
Histone H3K14 acetyltransferase activity is a key epigenetic mechanism that regulates gene expression by modifying chromatin structure. The deposition of H3K14ac is associated with open, transcriptionally active chromatin and is critical for normal development and cellular homeostasis. Dysregulation of this activity has been implicated in a wide range of diseases, particularly cancer, where aberrant H3K14 acetylation can drive oncogenic gene expression programs. For example, KAT7-mediated H3K14 acetylation promotes colorectal cancer progression, and its inhibition reduces tumor growth. Moreover, environmental factors such as zinc deficiency can impair KAT7-dependent H3K14 acetylation, leading to pathophysiological consequences. Therefore, understanding GO:0036408 is essential for developing targeted therapies and for deciphering the epigenetic basis of disease.
• H3K14ac is a marker of active transcription and is enriched at promoters and enhancers.
• KAT7 (HBO1) is a major enzyme responsible for H3K14 acetyltransferase activity in humans.
• Targeting KAT7 inhibits colorectal cancer progression, highlighting its therapeutic potential.
• Zinc deficiency impairs KAT7-dependent H3K14 acetylation, linking nutrition to epigenetic regulation.
• In plants, HAF2 controls H3K14ac during ethylene responses, showing evolutionary conservation.
• Chemical inhibition of HAT activity can modulate H3K14ac in plant models.
• H3K14 acetylation is involved in oocyte aging in grass carp, affecting H4K12 acetylation patterns.
• HBO1 is a versatile acyltransferase critical for promoter histone acylations, including H3K14ac.
• Dysregulation of H3K14ac is associated with various cancers and developmental disorders.
• CRISPR-based models enable precise manipulation of H3K14 acetyltransferase genes for functional studies.
What Happens During histone H3K14 acetyltransferase activity?
Recognition of Histone H3 Substrate
In simple terms: The enzyme first binds to histone H3 and identifies lysine 14 as the target.
The acetyltransferase enzyme, such as KAT7 (HBO1), recognizes the histone H3 tail and specifically engages lysine 14. This specificity is mediated by the enzyme's catalytic domain and accessory subunits that confer substrate selectivity. Structural studies of MYST-family HATs have revealed a conserved catalytic core that accommodates the histone H3 peptide, positioning lysine 14 for acetyl transfer.
Acetyl-CoA Binding and Acetyl Transfer
In simple terms: The enzyme uses acetyl-CoA as a donor to add an acetyl group onto lysine 14.
Upon substrate binding, the enzyme binds the cofactor acetyl-CoA. The acetyl group is transferred from acetyl-CoA to the epsilon-amino group of lysine 14, forming H3K14ac and releasing coenzyme A. This reaction is catalyzed by a conserved glutamate residue that acts as a general base. The activity is highly specific for lysine 14, as mutations of this residue abolish acetylation.
Chromatin Association and Promoter Occupancy
In simple terms: The enzyme works within chromatin, often at gene promoters to turn on genes.
H3K14 acetyltransferase activity occurs in the context of chromatin. KAT7/HBO1 is recruited to promoters by transcription factors and associates with the MYST complex, leading to localized H3K14ac and transcriptional activation. Genome-wide studies have shown that HBO1 is critical for promoter histone acylations, including H3K14ac, and its depletion reduces H3K14ac at target genes.
Regulation by Cellular Signals
In simple terms: The activity can be turned up or down by signals like zinc levels or oncogenic pathways.
H3K14 acetyltransferase activity is regulated by various cellular signals. For instance, zinc deficiency impairs KAT7-dependent H3K14 acetylation, suggesting a link between zinc homeostasis and this epigenetic mark. In cancer, KAT7 is often overexpressed, leading to increased H3K14ac and activation of oncogenic gene expression programs. Additionally, in plants, HAF2 associates with the PDC complex to control H3K14ac in response to ethylene.
Downstream Effects on Gene Expression
In simple terms: Adding acetyl groups to H3K14 helps open chromatin and turn on genes.
H3K14ac is recognized by bromodomain-containing proteins that recruit transcriptional machinery, leading to increased gene expression. This mark is associated with active enhancers and promoters, and its deposition correlates with transcriptional output. Consequently, alterations in H3K14 acetyltransferase activity can lead to widespread changes in gene expression programs, contributing to diseases such as cancer.
Key Genes Involved in GO:0036408 histone H3K14 acetyltransferase activity
The following genes encode enzymes or associated proteins that carry out or regulate histone H3K14 acetyltransferase activity (GO:0036408).
| Gene | Major Role | Research Relevance |
|---|---|---|
| KAT7 (MYST2/HBO1) | Major histone acetyltransferase that deposits H3K14ac and other acyl marks at promoters | Target in colorectal cancer; regulates gene expression and development |
| KAT6A (MOZ) | MYST-family HAT that can acetylate H3K14 in some contexts | Implicated in leukemia and developmental disorders |
| KAT6B (MORF) | MYST-family HAT with H3K14 acetyltransferase activity | Associated with cancer and developmental syndromes |
| KAT5 (TIP60) | HAT that acetylates H3K14 and other lysines | Roles in DNA repair and cancer |
| EP300 (p300) | Transcriptional coactivator with HAT activity, can acetylate H3K14 | Broad roles in cancer and development |
| CREBBP (CBP) | HAT that acetylates H3K14 and other residues | Mutated in Rubinstein-Taybi syndrome and cancers |
| HAF2 | Plant homolog of KAT7 that controls H3K14ac and H3K23ac | Model for studying H3K14ac in ethylene responses |
| GCN5 (KAT2A) | HAT that can acetylate H3K14 in some complexes | Involved in transcriptional regulation and cancer |
| PCAF (KAT2B) | HAT with H3K14 acetyltransferase activity | Roles in cell cycle and differentiation |
| MYST1 (KAT8) | MYST-family HAT that can acetylate H3K14 | Implicated in chromatin regulation and cancer |
| JADE1 | Subunit of HBO1 complex that stimulates H3K14 acetylation | Regulates HBO1 activity and gene expression |
| JADE2 | Subunit of HBO1 complex involved in H3K14ac | Modulates HBO1 substrate specificity |
| BRPF1 | Scaffold protein in HBO1 complex that enhances H3K14 acetylation | Required for HBO1-mediated H3K14ac |
| BRPF2 | Component of HBO1 complex | Regulates HAT complex assembly |
| BRPF3 | Component of HBO1 complex | Modulates H3K14 acetylation |
| ING4 | Subunit of HBO1 complex that recognizes H3K4me3 and promotes H3K14ac | Links chromatin marks to H3K14 acetylation |
| ING5 | Subunit of HBO1 complex | Involved in H3K14ac regulation |
| EAF6 | Component of HBO1 complex | Essential for HAT complex integrity |
How Is histone H3K14 acetyltransferase activity Regulated?
Histone H3K14 acetyltransferase activity is regulated at multiple levels. The catalytic activity of KAT7/HBO1 is dependent on its association with accessory subunits such as JADE1/2, BRPF1/2/3, ING4/5, and EAF6, which form the HBO1 complex and modulate substrate specificity and activity. Post-translational modifications of the enzyme and its subunits can also influence activity. Cellular signals, including zinc availability, can impact KAT7-dependent H3K14 acetylation; zinc deficiency impairs this activity, linking nutritional status to epigenetic regulation. In cancer, oncogenic pathways can upregulate KAT7 expression, leading to increased H3K14ac and activation of pro-tumorigenic gene expression programs. Additionally, in plants, the HAF2-PDC association controls H3K14ac in response to ethylene, demonstrating hormonal regulation of this activity.
histone H3K14 acetyltransferase activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| KAT7 (HBO1) | Colorectal cancer progression | KAT7 knockout or overexpression in colorectal cancer cell lines; xenograft models |
| KAT7 (HBO1) | Zinc deficiency-induced pathophysiology | Zinc-deficient cell culture and animal models with KAT7 knockdown |
| HAF2 | Ethylene response in plants | Arabidopsis haf2 mutants and overexpression lines |
| EP300/CREBBP | Rubinstein-Taybi syndrome and cancers | Patient-derived cells and CRISPR knock-in models |
| KAT6A/KAT6B | Leukemia and developmental disorders | Knockout and point-mutation models in hematopoietic cells |
H3K14 Acetylation in Cancer
Aberrant histone H3K14 acetylation is increasingly recognized as a driver of cancer. KAT7 (HBO1) is overexpressed in several cancers, including colorectal cancer, where it promotes tumor progression by depositing H3K14ac at oncogenic promoters. Targeting KAT7 with inhibitors or genetic knockdown reduces H3K14ac and inhibits cancer cell proliferation, suggesting that H3K14 acetyltransferase activity is a potential therapeutic target. Furthermore, H3K14ac is a marker of active transcription that can be hijacked by cancer cells to sustain oncogenic gene expression programs.
Zinc Deficiency and Epigenetic Dysregulation
Zinc is an essential micronutrient, and its deficiency has been linked to impaired KAT7-dependent H3K14 acetylation. This impairment can lead to altered gene expression and pathophysiological outcomes, including developmental defects and increased cancer risk. The connection between zinc status and H3K14ac highlights the importance of nutritional factors in epigenetic regulation and suggests that zinc supplementation might modulate this activity in disease contexts.
H3K14ac in Plant Development and Stress Responses
In plants, H3K14 acetylation is involved in ethylene responses, with HAF2 (a KAT7 homolog) associating with the PDC complex to control H3K14ac and H3K23ac. Chemical inhibition of HAT activity in Arabidopsis affects H3K14ac, demonstrating the utility of plant models for studying this modification. These findings underscore the evolutionary conservation of H3K14 acetyltransferase activity and its role in developmental and environmental responses.
H3K14ac in Oocyte Aging
In grass carp, post-ovulatory oocyte aging is associated with changes in H4K12 acetylation patterns and histone acetyltransferase activity, suggesting a role for HATs in reproductive aging. While this study focused on H4K12ac, it highlights the broader importance of histone acetylation, including H3K14ac, in oocyte quality and aging.
From histone H3K14 acetyltransferase activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of KAT7 reduce H3K14ac and inhibit tumor growth? | KAT7 knockout in cancer cell lines and mouse xenografts |
| What is the catalytic mechanism of H3K14 acetylation by HBO1? | Point mutations in the catalytic domain of KAT7 (e.g., glutamate to glutamine) |
| How does zinc deficiency affect KAT7-dependent H3K14ac? | Zinc-deficient cell culture with KAT7 knockdown or knockout |
| Can a tagged KAT7 be used to map its genomic binding sites? | Knock-in of epitope-tagged KAT7 (e.g., FLAG-HA) via CRISPR |
| Does overexpression of HAF2 increase H3K14ac in plants? | HAF2 overexpression in Arabidopsis |
| What are the downstream genes regulated by H3K14ac in cancer? | KAT7 knockout followed by RNA-seq and ChIP-seq |
How to Study the histone H3K14 acetyltransferase activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| ChIP-qPCR | Enrichment of H3K14ac at specific loci | Validate H3K14ac at candidate promoters after KAT7 knockout |
| ChIP-seq | Genome-wide distribution of H3K14ac | Map H3K14ac across the genome and correlate with gene expression |
| In vitro HAT assay | Enzymatic activity of H3K14 acetyltransferases | Test inhibitors or mutant enzymes |
| Western blot | Global levels of H3K14ac | Assess changes in H3K14ac upon gene manipulation |
| RNA-seq | Transcriptional changes | Identify genes regulated by H3K14ac |
| Mass spectrometry | Quantification of histone modifications | Global profiling of acetylation including H3K14ac |
| CRISPR screen | Genes required for H3K14ac or cell growth | Discover novel regulators of H3K14 acetylation |
| Immunofluorescence | Nuclear localization of H3K14ac | Visualize H3K14ac patterns in cells |
Chromatin Immunoprecipitation (ChIP) for H3K14ac
ChIP using antibodies specific to H3K14ac allows mapping of this mark across the genome. This method can identify promoters and enhancers enriched for H3K14ac and assess changes upon knockout or overexpression of H3K14 acetyltransferases such as KAT7. Combining ChIP with sequencing (ChIP-seq) provides genome-wide profiles and reveals direct target genes.
Histone Acetyltransferase Activity Assays
In vitro HAT assays using recombinant enzymes and histone substrates (or peptides) measure the catalytic transfer of acetyl groups from acetyl-CoA to H3K14. These assays can be used to test inhibitors, assess mutant enzymes, and determine kinetic parameters. Radioactive or fluorescent acetyl-CoA derivatives enable sensitive detection.
CRISPR-Based Genetic Screens
Genome-wide CRISPR knockout or activation screens can identify genes that regulate H3K14ac levels or that are required for the growth of cells dependent on this activity. Such screens can uncover novel components of the H3K14 acetyltransferase pathway and potential drug targets.
Transcriptomics and Proteomics
RNA-seq after knockout or knockdown of H3K14 acetyltransferases reveals transcriptional changes driven by loss of H3K14ac. Proteomics approaches, such as mass spectrometry, can quantify global histone acetylation changes and identify interacting proteins in HAT complexes.
How CRISPR Can Be Used to Study GO:0036408 histone H3K14 acetyltransferase activity
Knockout
CRISPR knockout of H3K14 acetyltransferase genes such as KAT7 (HBO1) is a powerful approach to study loss-of-function phenotypes. KAT7 knockout in colorectal cancer cells reduces H3K14ac and inhibits proliferation, validating its oncogenic role. Knockout models can also be used to assess the contribution of H3K14ac to gene expression programs and to identify synthetic lethal interactions.
Point Mutation
Introducing point mutations in the catalytic domain of H3K14 acetyltransferases (e.g., the conserved glutamate residue in KAT7) via CRISPR can dissect the enzymatic activity from scaffolding functions. Such mutants can be knocked into the endogenous locus to study the specific contribution of H3K14 acetylation to cellular processes.
Knock-in
CRISPR knock-in of epitope tags (e.g., FLAG, HA) or fluorescent proteins into H3K14 acetyltransferase genes allows for affinity purification of the enzyme complex and mapping of its genomic binding sites. Tagged KAT7 knock-in cells have been used to characterize the HBO1 complex and its role in promoter acetylation.
Overexpression
CRISPR activation (CRISPRa) or cDNA overexpression can be used to increase the levels of H3K14 acetyltransferases. Overexpression of HAF2 in Arabidopsis increases H3K14ac and affects ethylene responses, demonstrating the utility of gain-of-function models. In cancer cells, overexpression of KAT7 can drive increased H3K14ac and oncogenic gene expression.
How EDITGENE Supports histone H3K14 acetyltransferase activity Research
Researchers studying histone H3K14 acetyltransferase activity-related genes often need to determine whether a candidate gene is causally involved in the deposition of H3K14ac and its downstream biological effects. EDITGENE provides a comprehensive suite of CRISPR-based services to enable such investigations, from gene knockout to precise point mutations and knock-in of reporters or tags.
Contact EDITGENE today to design your custom CRISPR model for histone H3K14 acetyltransferase activity research.
Frequently Asked Questions About histone H3K14 acetyltransferase activity
What is histone H3K14 acetyltransferase activity?
It is the enzymatic activity defined by GO:0036408 that transfers an acetyl group from acetyl-CoA to lysine 14 of histone H3, producing H3K14ac.
What genes are involved in histone H3K14 acetyltransferase activity?
Key genes include KAT7 (HBO1), KAT6A, KAT6B, KAT5, EP300, CREBBP, and in plants HAF2.
What is the role of H3K14 acetylation in cancer?
H3K14ac is associated with active transcription and can drive oncogenic gene expression; KAT7 overexpression promotes colorectal cancer, and targeting KAT7 inhibits tumor growth.
How is H3K14 acetyltransferase activity regulated?
It is regulated by complex formation with subunits like JADE1/2, BRPF1/2/3, ING4/5, and EAF6, as well as by cellular signals such as zinc availability.
What diseases are linked to H3K14 acetylation?
Cancers such as colorectal cancer, developmental disorders, and conditions related to zinc deficiency have been linked to altered H3K14ac.
How can I study H3K14 acetyltransferase activity in the lab?
Common methods include ChIP-seq, in vitro HAT assays, Western blot for H3K14ac, and CRISPR knockout or overexpression of HAT genes.
What is the difference between H3K14ac and other histone acetylations?
H3K14ac specifically refers to acetylation at lysine 14 of histone H3, while other marks like H3K9ac or H4K12ac involve different residues and are deposited by distinct enzymes.
Can CRISPR be used to study H3K14 acetyltransferase activity?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models allow precise manipulation of HAT genes to study H3K14ac function.
What is the evolutionary conservation of H3K14 acetyltransferase activity?
It is conserved from plants to humans; for example, HAF2 in Arabidopsis is a homolog of KAT7 and controls H3K14ac during ethylene responses.
What are the potential therapeutic implications of targeting H3K14 acetyltransferase activity?
Inhibiting KAT7/HBO1 to reduce H3K14ac is a promising strategy for cancer therapy, as it can suppress oncogenic gene expression and tumor growth.
Conclusion
Histone H3K14 acetyltransferase activity (GO:0036408) is a fundamental epigenetic mechanism that regulates gene expression by depositing the H3K14ac mark. Its dysregulation is implicated in cancer, developmental disorders, and nutritional stress responses, making it an attractive target for therapeutic intervention. The activity is carried out by a family of enzymes, most notably KAT7/HBO1, which functions within multi-subunit complexes to acetylate H3K14 at promoters. Advances in CRISPR-based genome editing have revolutionized the study of H3K14 acetyltransferase activity, enabling precise knockout, point mutation, knock-in, and overexpression models. These tools, combined with chromatin and transcriptomic analyses, will continue to uncover the molecular details and disease relevance of this modification. EDITGENE is committed to supporting researchers in this endeavor with tailored CRISPR services and bioinformatics solutions.
References
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