GO:0035175 histone H3S10 kinase activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0035175 histone H3S10 kinase activity describes the catalytic addition of a phosphate group to serine 10 of histone H3, a chromatin mark linked to transcription and chromosome dynamics.
• The reaction consumes ATP and produces ADP plus histone H3 phosphoserine 10, as defined by the QuickGO molecular function entry.
• Major experimental H3S10 kinases include Aurora kinase A and the Drosophila JIL-1 kinase, which phosphorylate H3S10 and influence transcription and heterochromatin.
• H3S10 phosphorylation is dynamically controlled by chromosomal targeting modules such as JASPer and by the COOH-terminal domain of JIL-1.
• Deregulated H3S10 phosphorylation and its kinases are implicated in cancer biology and therapy, making the term a target for epigenetic drug discovery.
• CRISPR knockout, point-mutation, knock-in, and overexpression models enable causal testing of H3S10 kinase genes in chromatin and disease contexts.
Description
Histone H3S10 kinase activity (GO:0035175) is a molecular function that catalyzes the transfer of a phosphate group from ATP to serine 10 of histone H3, generating phospho-H3S10 and ADP. This modification is a well-studied chromatin mark that participates in transcriptional regulation and chromosome architecture, and its writers are therefore central to epigenetic control. Because the mark is reversible and context-dependent, the kinases that deposit it are tightly regulated and targeted to specific chromosomal regions. Researchers study GO:0035175 to understand how chromatin states are established and remodeled, and to evaluate whether H3S10 kinases contribute to disease-associated transcriptional programs. The term is also relevant to DNA damage signaling and post-replicative chromatin restoration, where H3S10 phosphorylation intersects with ATM signaling and H3K9 methylation pathways.
histone H3S10 kinase activity At A Glance
| GO ID | GO:0035175 |
|---|---|
| GO term | histone H3S10 kinase activity |
| Ontology | molecular_function |
| Synonym | histone kinase activity (H3-S10 specific); histone serine kinase activity (H3-S10 specific); histone-serine kinase activity (H3-S10 specific) |
| Major function | Phosphorylation of histone H3 at serine 10 using ATP, producing phospho-H3S10 and ADP |
| Reaction | histone H3-serine (position 10) + ATP = histone H3-phosphoserine (position 10) + ADP |
| Substrate | Histone H3 serine 10 |
| Cofactor | ATP as phosphate donor |
| Representative kinases | Aurora kinase A; Drosophila JIL-1 |
What Is GO:0035175?
GO:0035175 histone H3S10 kinase activity is defined as catalysis of the reaction: histone H3-serine (position 10) + ATP = histone H3-phosphoserine (position 10) + ADP. In other words, it is the enzyme activity that adds a phosphate group specifically to serine 10 of histone H3, using ATP as the phosphate donor.
Why Is histone H3S10 kinase activity Important in Cell Biology?
GO:0035175 is important because phosphorylation of histone H3 at serine 10 is a dynamic chromatin mark that influences transcription, heterochromatin organization, and the response to DNA damage, and because the kinases that carry out this reaction are frequently deregulated in cancer. Understanding this activity helps explain how chromatin states are written and erased, and it provides a mechanistic entry point for epigenetic therapies that target H3S10 kinases.
• Defines a specific chromatin-writing activity that converts ATP into a phospho-mark on histone H3 serine 10.
• Links directly to transcriptional regulation by Aurora kinase A, which phosphorylates H3S10 to modulate gene expression.
• Controls heterochromatin spreading and dimethyl H3K9 modifications through the JIL-1 kinase in Drosophila.
• Is targeted to chromatin by dedicated domains such as the JIL-1 COOH-terminal domain and the JASPer factor.
• Ectopic H3S10 phosphorylation can remodel chromatin structure, showing that the mark is functionally consequential.
• Intersects with ATM signaling and DNA damage-induced transcription stress.
• Participates in post-replicative restoration of H3K9me3 through RIF1-dependent pathways.
• Is a candidate therapeutic axis in cancer because H3S10 kinases and the mark are deregulated in tumors.
• Provides a readout for epigenetic drug screens and for CRISPR-based chromatin perturbation studies.
• Enables mechanistic dissection of kinase-substrate specificity when combined with knockout and point-mutation models.
Molecular Mechanism of histone H3S10 kinase activity
Substrate recognition and chromatin targeting
In simple terms: The kinase must first find histone H3 and bind the right spot on chromatin.
H3S10 kinases are targeted to chromatin through dedicated interaction modules. The COOH-terminal domain of the Drosophila JIL-1 kinase interacts with histone H3 and is required for correct targeting to chromatin. In addition, the JASPer factor controls interphase H3S10 phosphorylation by the chromosomal kinase JIL-1, illustrating that targeting is a regulated step rather than a constitutive property of the kinase.
Catalytic transfer of phosphate from ATP to serine 10
In simple terms: The kinase uses ATP to attach a phosphate tag onto serine 10 of histone H3.
The defining chemistry of GO:0035175 is the transfer of a phosphate group from ATP to histone H3 serine 10, yielding phospho-H3S10 and ADP. Aurora kinase A can carry out this reaction and thereby mediate transcriptional regulation, demonstrating that H3S10 phosphorylation is directly coupled to gene expression control.
Chromatin remodeling and heterochromatin regulation
In simple terms: Adding the phosphate tag changes how chromatin is packaged and read.
Ectopic histone H3S10 phosphorylation causes chromatin structure remodeling in Drosophila, showing that the mark can alter higher-order chromatin organization. The JIL-1 H3S10 kinase also regulates dimethyl H3K9 modifications and heterochromatic spreading, linking H3S10 phosphorylation to the establishment of repressive chromatin domains.
Crosstalk with DNA damage and replication-associated chromatin
In simple terms: The mark also participates in how cells respond to DNA damage and restore chromatin after replication.
Crosstalk between chromatin state and ATM signalling in DNA damage-induced transcription stress places H3S10 phosphorylation within the DNA damage response network. In addition, RIF1 orchestrates a multi-step restoration of post-replicative H3K9me3, a process that intersects with H3S10 phosphorylation-dependent chromatin states.
Key Genes Involved in GO:0035175 histone H3S10 kinase activity
The following genes and proteins are experimentally linked to histone H3S10 kinase activity, either as catalytic kinases, targeting factors, or chromatin crosstalk regulators.
| Gene | Major Role | Research Relevance |
|---|---|---|
| AURKA | Aurora kinase A; phosphorylates H3S10 and mediates transcriptional regulation | Cancer biology and mitotic/transcriptional control |
| JIL-1 | Drosophila histone H3S10 kinase; regulates dimethyl H3K9 and heterochromatic spreading | Chromatin domain formation and heterochromatin studies |
| JASPer | Controls interphase H3S10 phosphorylation by chromosomal kinase JIL-1 | Targeting and regulation of H3S10 kinase activity |
| H3 | Histone H3 substrate; serine 10 is the phospho-acceptor | Substrate mutation and mark-specific assays |
| ATM | DNA damage signaling kinase that crosstalks with chromatin state | DNA damage-induced transcription stress |
| RIF1 | Orchestrates post-replicative restoration of H3K9me3 | Replication-coupled chromatin restoration |
| H3K9me2/3 | Repressive chromatin mark regulated by JIL-1 H3S10 kinase | Heterochromatin spreading assays |
| JIL-1 CTD | COOH-terminal domain of JIL-1 that binds histone H3 for chromatin targeting | Domain mapping and targeting studies |
| Aurora kinase family | Related kinases with H3S10 phosphorylation capacity | Kinase inhibitor and selectivity studies |
| Chromosomal kinase complexes | Multi-protein assemblies that deliver H3S10 kinase activity to chromatin | Complex purification and imaging |
| Phospho-H3S10 readers | Proteins that interpret the H3S10ph mark | Epigenetic reader discovery |
| Phosphatases | Enzymes that reverse H3S10 phosphorylation | Dynamic mark turnover studies |
| Transcription elongation machinery | Couples H3S10 phosphorylation to active transcription | RNA polymerase II and transcription assays |
| Heterochromatin proteins | Effectors of H3K9 methylation affected by JIL-1 | Position-effect variegation and silencing |
| DNA damage response factors | ATM-pathway components that intersect with H3S10ph | Damage-response transcription profiling |
| Replication-associated factors | RIF1-pathway proteins restoring H3K9me3 | Post-replicative chromatin assays |
How Is histone H3S10 kinase activity Regulated?
H3S10 kinase activity is regulated at multiple levels. Targeting to chromatin depends on interaction modules such as the JIL-1 COOH-terminal domain and on factors like JASPer that control interphase H3S10 phosphorylation. The activity is also embedded in signaling networks: ATM signaling crosstalks with chromatin state during DNA damage-induced transcription stress, and post-replicative restoration of H3K9me3 by RIF1 provides a replication-coupled context for H3S10 phosphorylation-dependent chromatin states. In cancer, H3S10 kinases and the mark itself are deregulated, making their regulation a therapeutic focus.
histone H3S10 kinase activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| AURKA | Cancer; transcriptional regulation via H3S10 phosphorylation | Cancer cell line knockout and overexpression |
| JIL-1 | Heterochromatin spreading and gene silencing | Drosophila mutant and rescue models |
| ATM | DNA damage-induced transcription stress | ATM knockout cell lines with damage treatment |
| RIF1 | Post-replicative H3K9me3 restoration | RIF1 knockout and knock-in cell lines |
| H3 | Chromatin structure remodeling | Histone H3 point-mutant knock-in |
Cancer and epigenetic deregulation
H3S10 phosphorylation and H3S10 kinases are deregulated in cancer, and the mark has been proposed as a target in cancer biology and therapy. Aurora kinase A, a representative H3S10 kinase, mediates transcriptional regulation that can support oncogenic gene expression programs. These observations motivate CRISPR-based tests of whether specific H3S10 kinases are causally required for tumor cell phenotypes.
DNA damage response and genome stability
Crosstalk between chromatin state and ATM signalling during DNA damage-induced transcription stress links H3S10 phosphorylation to genome-stability pathways. Because ATM signaling coordinates transcription and repair, perturbations of H3S10 kinase activity may alter cellular responses to DNA damage.
Replication-associated chromatin restoration
RIF1 orchestrates a multi-step restoration of post-replicative H3K9me3, a process that intersects with H3S10 phosphorylation-dependent chromatin states. Defects in this restoration pathway could contribute to epigenetic instability, making it relevant to diseases characterized by chromatin dysfunction.
From histone H3S10 kinase activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is the kinase required for H3S10 phosphorylation? | CRISPR knockout of the candidate H3S10 kinase |
| Does serine 10 of histone H3 carry the mark? | H3S10 point-mutation knock-in |
| Can a tagged kinase be tracked to chromatin? | Tagged knock-in of the kinase |
| Does overexpression alter chromatin state? | Overexpression of the H3S10 kinase |
| Which domains target the kinase to chromatin? | Domain-deletion knock-in or knockout |
| Does the mark crosstalk with DNA damage signaling? | ATM-pathway knockout with damage treatment |
How to Study the histone H3S10 kinase activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Phospho-H3S10 immunoblotting | Levels of the H3S10 phosphorylation mark | Kinase perturbation validation |
| Chromatin immunoprecipitation | Chromatin association of kinases and marks | Targeting domain mapping |
| RNA-seq | Transcriptional changes after kinase perturbation | Aurora kinase A target gene discovery |
| Drosophila genetics | Heterochromatin spreading and silencing phenotypes | JIL-1 loss- and gain-of-function |
| Chromatin structure assays | Higher-order chromatin remodeling | Ectopic H3S10 phosphorylation studies |
| DNA damage transcription assays | ATM-dependent transcription stress | Chromatin-ATM crosstalk |
| Replication-coupled chromatin assays | Post-replicative H3K9me3 restoration | RIF1 pathway studies |
| Kinase inhibitor profiling | Selectivity and cellular effects of H3S10 kinase inhibition | Cancer epigenetic drug testing |
Chromatin immunoprecipitation and phospho-specific detection
Phospho-H3S10 can be detected with modification-specific antibodies, and chromatin association of H3S10 kinases can be mapped by chromatin immunoprecipitation. The COOH-terminal domain of JIL-1 was shown to interact with histone H3 and to be required for correct targeting to chromatin, illustrating how domain-focused ChIP and binding assays define targeting determinants.
Genetic perturbation in model organisms
Drosophila genetics has been central to defining H3S10 kinase function. JIL-1 regulates dimethyl H3K9 modifications and heterochromatic spreading, and ectopic H3S10 phosphorylation causes chromatin structure remodeling, providing phenotypic readouts for loss- and gain-of-function studies. JASPer controls interphase H3S10 phosphorylation by JIL-1, offering a second genetic entry point.
Transcriptional and signaling profiling
Because Aurora kinase A mediates transcriptional regulation through H3S10 phosphorylation, RNA-based profiling after kinase perturbation can identify downstream gene expression changes. Crosstalk with ATM signaling during DNA damage-induced transcription stress can be interrogated by combining damage treatments with chromatin and transcription readouts.
Replication and chromatin restoration assays
RIF1-dependent restoration of post-replicative H3K9me3 provides a framework for studying how H3S10 phosphorylation intersects with replication-coupled chromatin assembly. Time-course chromatin assays after replication can resolve the sequence of mark restoration.
How CRISPR Can Be Used to Study GO:0035175 histone H3S10 kinase activity
Knockout
CRISPR knockout of candidate H3S10 kinases such as AURKA or JIL-1 orthologs allows direct testing of whether the kinase is required for phospho-H3S10 and for downstream transcriptional or heterochromatin phenotypes. Knockout models are also useful for validating crosstalk with ATM signaling and replication-associated chromatin restoration.
Point Mutation
Point-mutation knock-in of histone H3 at serine 10 can test whether the phospho-acceptor residue is required for chromatin remodeling and for mark-dependent phenotypes. Catalytic-dead point mutations in the kinase domain can separate enzymatic activity from scaffolding functions.
Knock-in
Tagged knock-in of H3S10 kinases enables tracking of chromatin targeting and complex assembly, building on evidence that the JIL-1 COOH-terminal domain interacts with histone H3 and is required for correct targeting. Knock-in of targeting-domain variants can dissect which domains are necessary for H3S10 phosphorylation in vivo.
Overexpression
Overexpression of H3S10 kinases can induce ectopic phosphorylation and chromatin structure remodeling, providing a gain-of-function counterpart to knockout studies. Overexpression models are also useful for testing whether increased H3S10 kinase activity drives transcriptional programs relevant to cancer.
How EDITGENE Supports histone H3S10 kinase activity Research
Researchers studying histone H3S10 kinase activity-related genes often need to determine whether a candidate gene is causally involved in depositing or interpreting the H3S10 phosphorylation mark, and whether that activity changes chromatin state, transcription, or disease-relevant phenotypes. EDITGENE provides the CRISPR cell models and screening services needed to move from correlation to causation in this chromatin pathway.
Contact EDITGENE today to design your custom CRISPR model for histone H3S10 kinase activity research.
Frequently Asked Questions About histone H3S10 kinase activity
What is histone H3S10 kinase activity?
It is the enzyme activity defined by GO:0035175 that transfers a phosphate group from ATP to serine 10 of histone H3, producing phospho-H3S10 and ADP.
What genes are involved in histone H3S10 kinase activity?
Key genes include AURKA, which encodes Aurora kinase A and phosphorylates H3S10, and Drosophila JIL-1, a chromosomal H3S10 kinase, along with targeting factors such as JASPer.
What is the GO ID for histone H3S10 kinase activity?
The Gene Ontology identifier is GO:0035175, classified under molecular_function.
How is H3S10 phosphorylation targeted to chromatin?
Targeting depends on interaction modules such as the JIL-1 COOH-terminal domain, which binds histone H3, and on factors like JASPer that control interphase H3S10 phosphorylation.
Why is histone H3S10 kinase activity important in cancer?
H3S10 phosphorylation and its kinases are deregulated in cancer, and the mark has been discussed as a target in cancer biology and therapy. Aurora kinase A also mediates transcriptional regulation through H3S10 phosphorylation.
Does H3S10 phosphorylation affect heterochromatin?
Yes. The JIL-1 H3S10 kinase regulates dimethyl H3K9 modifications and heterochromatic spreading, and ectopic H3S10 phosphorylation causes chromatin structure remodeling.
How does H3S10 phosphorylation crosstalk with DNA damage signaling?
Chromatin state crosstalks with ATM signalling during DNA damage-induced transcription stress, linking H3S10 phosphorylation to the DNA damage response.
Is H3S10 phosphorylation involved in replication-associated chromatin restoration?
RIF1 orchestrates a multi-step restoration of post-replicative H3K9me3, a process that intersects with H3S10 phosphorylation-dependent chromatin states.
What experimental models are used to study H3S10 kinase activity?
Common models include Drosophila genetics for JIL-1 and JASPer, cancer cell lines for Aurora kinase A, and CRISPR knockout, point-mutation, knock-in, and overexpression systems.
Can CRISPR be used to study histone H3S10 kinase activity?
Yes. CRISPR knockout, point-mutation, knock-in, and overexpression models allow causal testing of H3S10 kinases and the H3 serine 10 phospho-acceptor in chromatin and disease contexts.
Conclusion
GO:0035175 histone H3S10 kinase activity defines a specific chromatin-writing reaction in which ATP is used to phosphorylate histone H3 serine 10. Experimental work on Aurora kinase A, JIL-1, JASPer, and their crosstalk with ATM signaling and replication-associated chromatin restoration has established this activity as a central node in transcriptional and chromatin regulation. Because the mark and its kinases are deregulated in cancer, the pathway is a promising target for epigenetic research and therapeutic development. CRISPR-based knockout, point-mutation, knock-in, and overexpression models provide the causal tools needed to dissect this activity in health and disease.
References
- 1. Albig C et al.. 2019. JASPer controls interphase histone H3S10 phosphorylation by chromosomal kinase JIL-1 in Drosophila.. Nat Commun 10(1):5343 PMID: 31767855
- 2. Komar D et al.. 2020. Rebelled epigenome: histone H3S10 phosphorylation and H3S10 kinases in cancer biology and therapy.. Clin Epigenetics 12(1):147 PMID: 33054831
- 3. Bao X et al.. 2008. The COOH-terminal domain of the JIL-1 histone H3S10 kinase interacts with histone H3 and is required for correct targeting to chromatin.. J Biol Chem 283(47):32741-50 PMID: 18819909
- 4. Kim SR et al.. 2016. H3S10 phosphorylation-mediated transcriptional regulation by Aurora kinase A.. Biochem Biophys Res Commun 469(1):22-28 PMID: 26607113
- 5. Zhang W et al.. 2006. The JIL-1 histone H3S10 kinase regulates dimethyl H3K9 modifications and heterochromatic spreading in Drosophila.. Development 133(2):229-35 PMID: 16339185
- 6. Salas-Armenteros I et al.. 2025. Crosstalk between chromatin state and ATM signalling in DNA damage-induced transcription stress.. EMBO J 44(19):5564-5594 PMID: 40859031
- 7. Deng H et al.. 2008. Ectopic histone H3S10 phosphorylation causes chromatin structure remodeling in Drosophila.. Development 135(4):699-705 PMID: 18199578
- 8. Chen N et al.. 2025. RIF1 orchestrates a multi-step restoration of post-replicative H3K9me3.. bioRxiv PMID: 40791448
