GO:0140713 histone chaperone activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0140713 histone chaperone activity is a molecular function defined as binding to and carrying a histone or histone complex to unload or deposit it as a nucleosome.
• Histone chaperones such as HIRA, SPT6, SPT2, APLF, NRP1 and ATAD2 control chromatin assembly, histone turnover and genome stability.
• Aberrant histone chaperone activity is increasingly linked to cancer pathology, including prostate cancer, senescence-associated inflammation and centrosome instability.
• Histone chaperone activity is regulated by splicing, post-translational modification, protein-protein interactions and chromatin-bound turnover.
• CRISPR knockout, point-mutation, knock-in and overexpression models are essential to test causality of chaperone genes in chromatin and disease phenotypes.
• EDITGENE provides end-to-end CRISPR cell model and library screening services to study histone chaperone activity in disease-relevant contexts.
Description
GO:0140713 histone chaperone activity is a molecular function that describes the binding and carrying of a histone or histone complex to unload or deposit it as a nucleosome. This activity is central to chromatin dynamics because it determines where and when nucleosomes are assembled, disassembled or replaced, thereby influencing transcription, replication, DNA repair and genome stability. Histone chaperones are not merely passive carriers; they coordinate with chromatin remodelers, transcription factors and signaling proteins to maintain the steady state of chromatin. Researchers study histone chaperone activity because its dysregulation is associated with cancer, senescence, inflammation and developmental defects. For example, the HIRA chaperone complex is implicated in prostate cancer progression through AR and E2F activity, while APLF kinase activity maintains centrosome homeostasis in embryonic stem cells. SPT6 and SPT2 control chromatin structure in metazoans, and their loss alters gene expression and genome integrity. ATAD2 mediates chromatin-bound histone chaperone turnover, linking chaperone dynamics to oncogenic transcription. Understanding GO:0140713 therefore requires integrating structural, biochemical and genetic approaches, including CRISPR-based models, to define how chaperones recognize histones and deposit them at specific genomic loci.
histone chaperone activity At A Glance
| GO ID | GO:0140713 |
|---|---|
| GO term | histone chaperone activity |
| Ontology | molecular_function |
| Synonym | histone carrier activity; nucleosome remodeling activity |
| Definition | Binding to and carrying a histone or a histone complex to unload or deposit it as a nucleosome; the histone can be newly synthesized or result from nucleosome disassembly. |
| Major function | Histone binding, histone transfer, nucleosome assembly and disassembly, chromatin homeostasis. |
| Representative proteins | HIRA, SPT6, SPT2, APLF, NRP1, ATAD2. |
| Disease relevance | Cancer, senescence-associated inflammation, centrosome instability, developmental defects. |
| Research methods | CRISPR KO/point mutation/knock-in/overexpression, histone-binding assays, ChIP-seq, proteomics. |
What Is GO:0140713?
In our own words, GO:0140713 histone chaperone activity is the function of a protein that binds a histone or a histone complex and carries it to a destination where the histone is unloaded or deposited as part of a nucleosome. The histone cargo can be newly synthesized or can come from a nucleosome that has been disassembled, either spontaneously or with the help of another histone chaperone. This activity is therefore distinct from histone modification enzymes and from ATP-dependent chromatin remodelers, although it often cooperates with them. The QuickGO definition emphasizes binding and carrying, not catalysis, so the function is typically measured by histone-binding assays, nucleosome assembly assays and chromatin occupancy studies.
Why Is histone chaperone activity Important in Cell Biology?
Histone chaperone activity is important because it governs the fundamental step of nucleosome assembly and disassembly, which in turn controls access to DNA for transcription, replication and repair. Without proper chaperone function, cells accumulate aberrant chromatin states, lose genome stability and misregulate gene expression programs. The clinical relevance is broad: HIRA splicing and function are linked to prostate cancer and senescence-associated inflammation, APLF maintains centrosome steady state in stem cells, and ATAD2-mediated chaperone turnover supports oncogenic transcription. Thus, GO:0140713 sits at the intersection of chromatin biology, cancer and regenerative medicine, making it a high-value target for mechanistic and therapeutic research.
• Controls nucleosome assembly and disassembly, affecting transcription, replication and DNA repair.
• Regulates chromatin accessibility and gene expression programs in development and disease.
• Dysregulation is linked to prostate cancer through HIRA-AR/E2F axis.
• Implicated in senescence-associated inflammation via HIRA, PML and p62/SQSTM1.
• APLF kinase activity maintains centrosome homeostasis in mouse embryonic stem cells.
• SPT6 and SPT2 control chromatin structure and function in Metazoa.
• ATAD2 mediates chromatin-bound histone chaperone turnover, supporting oncogenic transcription.
• NRP1 chaperone activity is blocked by cytochrome c, linking chromatin assembly to cell death signaling.
• Provides targets for CRISPR-based functional genomics in cancer and stem cell models.
• Enables therapeutic hypothesis testing through knockout, point-mutation and knock-in models.
What Happens During histone chaperone activity?
Histone recognition and binding
In simple terms: The chaperone first grabs the histone cargo.
Histone chaperones recognize histone proteins or histone complexes through dedicated binding surfaces. For example, the HIRA complex binds histones to deposit them in a replication-independent manner, while SPT6 uses its conserved N-terminal domain to control chromatin structure. SPT2 also binds histones to regulate chromatin in Metazoa. This step is essential because it determines which histone variant or modification state is carried and where it will be deposited.
Histone transfer and nucleosome deposition
In simple terms: The chaperone delivers the histone to DNA to build a nucleosome.
After binding, the chaperone transfers the histone to DNA or to a partially assembled nucleosome. This transfer can occur during DNA replication, transcription or repair, and it often requires cooperation with chromatin remodelers and other chaperones. The QuickGO definition explicitly includes unloading or depositing the histone as a nucleosome, which is the defining outcome of this activity. ATAD2-mediated turnover of chromatin-bound chaperones illustrates how deposition is balanced by removal to maintain dynamic chromatin.
Histone eviction and recycling
In simple terms: The chaperone can also take histones off DNA and recycle them.
Histone chaperones are not only depositors; they also accept histones that result from nucleosome disassembly, whether spontaneous or chaperone-assisted. This recycling function is critical during transcription and replication, when nucleosomes must be temporarily removed and then reassembled. The HIRA complex, for instance, participates in histone exchange and deposition in prostate cancer cells, and SPT6 controls chromatin structure through its N-terminal domain.
Coordination with signaling and cell state
In simple terms: Chaperone activity is tuned by signals and cell state.
Histone chaperone activity is coordinated with signaling pathways and cellular states. HIRA, PML and p62/SQSTM1 cooperate to regulate inflammation during cell senescence, and APLF kinase activity maintains centrosome steady state in mouse embryonic stem cells. NRP1 chaperone activity is blocked by cytochrome c, linking chromatin assembly to apoptotic signaling. These examples show that chaperone activity is not constitutive but is regulated by interacting proteins and post-translational events.
Key Genes Involved in GO:0140713 histone chaperone activity
The following genes and proteins are representative of histone chaperone activity (GO:0140713) and are supported by the verified literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| HIRA | Histone chaperone complex that deposits histones in replication-independent manner | Prostate cancer AR/E2F regulation, senescence inflammation |
| SPT6 | Conserved N-terminal domain controls chromatin structure | Chromatin structure and transcription regulation |
| SPT2 | Regulates chromatin structure and function in Metazoa | Metazoan chromatin and gene expression |
| APLF | Kinase activity maintains centrosome steady state | Embryonic stem cell centrosome homeostasis |
| NRP1 | Histone chaperone activity blocked by cytochrome c | Plant chromatin assembly and cell death signaling |
| ATAD2 | Mediates chromatin-bound histone chaperone turnover | Oncogenic transcription and chromatin dynamics |
| PML | Cooperates with HIRA and p62/SQSTM1 in senescence | Senescence-associated inflammation |
| SQSTM1/p62 | Cooperates with HIRA and PML in senescence | Inflammation and cell senescence |
| AR | Androgen receptor, linked to HIRA splicing in prostate cancer | Prostate cancer progression |
| E2F | Transcription factor linked to HIRA splicing in prostate cancer | Cell cycle and prostate cancer |
| SRSF6 | Modulates HIRA splicing | Splicing regulation in prostate cancer |
| Cytochrome c | Blocks NRP1 chaperone activity | Apoptosis and chromatin assembly crosstalk |
| H3 | Histone cargo for chaperones | Nucleosome assembly and chromatin |
| H4 | Histone cargo for chaperones | Nucleosome assembly and chromatin |
| H2A | Histone cargo for chaperones | Chromatin dynamics |
| H2B | Histone cargo for chaperones | Chromatin dynamics |
| ASF1 | Histone chaperone (general family member) | Chromatin assembly and cancer |
| CAF-1 | Histone chaperone (general family member) | Replication-coupled chromatin assembly |
How Is histone chaperone activity Regulated?
Histone chaperone activity is regulated at multiple levels. Splicing of HIRA is modulated by SRSF6, which affects AR and E2F activity in prostate cancer. Post-translational modifications such as kinase activity of APLF influence centrosome steady state in embryonic stem cells. Protein-protein interactions with PML and p62/SQSTM1 coordinate HIRA function during senescence-associated inflammation. Chromatin-bound turnover of chaperones is mediated by ATAD2, which controls the dynamic exchange of chaperones on chromatin. In plants, cytochrome c blocks NRP1 chaperone activity, providing a direct regulatory mechanism linking cell death signaling to chromatin assembly. These examples indicate that chaperone activity is tuned by splicing, modification, interaction partners and chromatin context.
histone chaperone activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| HIRA | Prostate cancer, senescence inflammation | CRISPR knockout and point-mutation in prostate cancer cell lines |
| ATAD2 | Oncogenic transcription | Knockout and overexpression in cancer cell lines |
| APLF | Centrosome instability in stem cells | Knockout in mouse embryonic stem cells |
| SPT6 | Chromatin structure defects | Knockout and tagged knock-in in metazoan cells |
| SPT2 | Metazoan chromatin dysfunction | Knockout in metazoan models |
Cancer
Aberrant histone chaperone activity is increasingly recognized in cancer pathology. HIRA splicing modulated by SRSF6 orchestrates AR and E2F activity in prostate cancer, linking chaperone function to oncogenic transcription. ATAD2 mediates chromatin-bound histone chaperone turnover and supports oncogenic programs. These findings suggest that chaperone activity can be targeted in cancers dependent on chromatin remodeling.
Senescence and inflammation
Histone chaperone HIRA, together with PML and p62/SQSTM1, coordinates inflammation during cell senescence. This indicates that chaperone activity influences the senescence-associated secretory phenotype and inflammatory signaling, which are relevant to aging and age-related diseases.
Stem cell and centrosome biology
APLF kinase activity maintains the steady state of centrosomes in mouse embryonic stem cells, connecting histone chaperone function to genome stability and stem cell maintenance. Disruption of this activity could affect cell division and developmental processes.
Cell death signaling
In Arabidopsis thaliana, cytochrome c blocks the histone chaperone activity of NRP1, providing a link between apoptotic signaling and chromatin assembly. This cross-talk highlights how chaperone activity can be modulated by cell death pathways.
From histone chaperone activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of HIRA affect AR/E2F target genes? | CRISPR knockout of HIRA in prostate cancer cells |
| Does APLF kinase activity maintain centrosomes? | Point-mutation of APLF kinase domain in mouse ES cells |
| How does SPT6 N-terminal domain control chromatin? | Tagged knock-in of SPT6 domains in metazoan cells |
| Does ATAD2 turnover regulate chaperone dynamics? | Overexpression and knockout of ATAD2 in cancer cells |
| Does NRP1 chaperone activity respond to cytochrome c? | Point-mutation of NRP1 in Arabidopsis |
| Does HIRA-PML-p62 cooperate in senescence? | Knockout of HIRA, PML or SQSTM1 in senescence models |
How to Study the histone chaperone activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Histone-binding assay | Direct chaperone-histone interaction | Testing mutant chaperone activity |
| Nucleosome assembly assay | Deposition of histones onto DNA | Functional validation of chaperones |
| ChIP-seq | Genomic localization of histones and chaperones | Mapping deposition and eviction sites |
| Proteomics | Interaction partners and complexes | Identifying regulatory networks |
| CRISPR knockout | Loss-of-function phenotypes | Testing causal roles in disease |
| CRISPR point mutation | Specific residue function | Dissecting catalytic or binding domains |
| CRISPR knock-in | Tagged or reporter alleles | Tracking chaperone dynamics |
| Overexpression | Gain-of-function effects | Modeling oncogenic chaperone activity |
Histone-binding and nucleosome assembly assays
Biochemical assays measure direct binding of chaperones to histones and their ability to deposit histones onto DNA. These assays are used to test whether mutations in chaperone domains affect GO:0140713 activity.
Chromatin immunoprecipitation and sequencing
ChIP-seq for histones and chaperones measures where histones are deposited or evicted across the genome. This is used to link chaperone activity to specific loci and transcription programs.
Proteomics and interaction mapping
Affinity purification and mass spectrometry identify chaperone interaction partners such as PML and p62/SQSTM1, revealing how chaperone activity is coordinated in cells.
CRISPR functional genomics
CRISPR knockout, point-mutation, knock-in and overexpression models test causality of chaperone genes in disease phenotypes, including cancer and stem cell maintenance.
How CRISPR Can Be Used to Study GO:0140713 histone chaperone activity
Knockout
CRISPR knockout of chaperone genes such as HIRA, APLF, SPT6 or ATAD2 can reveal loss-of-function phenotypes in chromatin structure, transcription and disease models. Knockout is typically used to test whether a chaperone is required for a specific process, such as AR/E2F activity in prostate cancer or centrosome maintenance in stem cells.
Point Mutation
Point mutations can be introduced into chaperone domains to dissect which residues are required for histone binding, transfer or regulation. For example, APLF kinase activity can be probed by point mutations in mouse embryonic stem cells, and NRP1 chaperone activity can be tested by mutating cytochrome c interaction sites.
Knock-in
Knock-in of tagged or reporter alleles allows tracking of chaperone localization, turnover and interaction with chromatin. Tagged SPT6 or ATAD2 alleles can be used to monitor chromatin-bound chaperone dynamics.
Overexpression
Overexpression of chaperones such as ATAD2 can model gain-of-function effects in cancer cells and test whether increased chaperone activity drives oncogenic transcription. Overexpression can also be combined with knockout to test dose-dependent effects.
How EDITGENE Supports histone chaperone activity Research
Researchers studying histone chaperone activity-related genes often need to determine whether a candidate gene is causally involved in chromatin regulation and disease. EDITGENE provides CRISPR-based cell model services to test knockout, point-mutation, knock-in and overexpression hypotheses in relevant cell types.
Contact EDITGENE today to design your custom CRISPR model for histone chaperone activity research.
Frequently Asked Questions About histone chaperone activity
What is GO:0140713 histone chaperone activity?
GO:0140713 histone chaperone activity is a molecular function defined as binding to and carrying a histone or histone complex to unload or deposit it as a nucleosome.
What genes are involved in histone chaperone activity?
Representative genes include HIRA, SPT6, SPT2, APLF, NRP1 and ATAD2, as well as general chaperones such as ASF1 and CAF-1.
How is histone chaperone activity regulated?
It is regulated by splicing, post-translational modifications, protein interactions and chromatin-bound turnover, as shown for HIRA, APLF, HIRA-PML-p62 and ATAD2.
Why is histone chaperone activity important in cancer?
Aberrant chaperone activity is linked to cancer pathology, including prostate cancer through HIRA-AR/E2F and oncogenic transcription via ATAD2.
What methods are used to study histone chaperone activity?
Common methods include histone-binding assays, nucleosome assembly assays, ChIP-seq, proteomics and CRISPR functional genomics.
Can CRISPR knockout be used to study histone chaperones?
Yes, CRISPR knockout of chaperone genes such as HIRA, APLF, SPT6 and ATAD2 is widely used to test loss-of-function phenotypes.
What is the role of HIRA in prostate cancer?
HIRA splicing modulated by SRSF6 orchestrates AR and E2F activity in prostate cancer.
How does APLF affect stem cells?
APLF kinase activity maintains the steady state of centrosomes in mouse embryonic stem cells.
What is the connection between histone chaperones and senescence?
HIRA, PML and p62/SQSTM1 cooperate to regulate inflammation during cell senescence.
What is the role of ATAD2 in chromatin?
ATAD2 mediates chromatin-bound histone chaperone turnover, supporting dynamic chromatin regulation.
Conclusion
GO:0140713 histone chaperone activity is a fundamental molecular function that controls histone binding, transfer and nucleosome assembly or disassembly. Its dysregulation is linked to cancer, senescence, centrosome instability and cell death signaling, making it a high-priority area for mechanistic and therapeutic research. CRISPR-based knockout, point-mutation, knock-in and overexpression models, combined with biochemical and genomic methods, provide a robust toolkit to dissect chaperone function and identify disease-relevant mechanisms. EDITGENE supports these efforts with comprehensive cell model and screening services.
References
- 1. Montero-Hidalgo AJ et al.. 2024. SRSF6 modulates histone-chaperone HIRA splicing to orchestrate AR and E2F activity in prostate cancer.. Sci Adv 10(40):eado8231 PMID: 39356765
- 2. Lee J et al.. 2024. Comparative Review on Cancer Pathology from Aberrant Histone Chaperone Activity.. Int J Mol Sci 25(12) PMID: 38928110
- 3. Rajam SM et al.. 2024. Kinase activity of histone chaperone APLF maintains steady state of centrosomes in mouse embryonic stem cells.. Eur J Cell Biol 103(3):151439 PMID: 38968704
- 4. Dasgupta N et al.. 2024. Histone chaperone HIRA, promyelocytic leukemia protein, and p62/SQSTM1 coordinate to regulate inflammation during cell senescence.. Mol Cell 84(17):3271-3287.e8 PMID: 39178863
- 5. González-Arzola K et al.. 2017. Histone chaperone activity of Arabidopsis thaliana NRP1 is blocked by cytochrome c.. Nucleic Acids Res 45(4):2150-2165 PMID: 27924001
- 6. Warner JL et al.. 2025. The histone chaperone Spt6 controls chromatin structure through its conserved N-terminal domain.. Mol Cell 85(18):3407-3424.e8 PMID: 40972526
- 7. Saredi G et al.. 2024. The histone chaperone SPT2 regulates chromatin structure and function in Metazoa.. Nat Struct Mol Biol 31(3):523-535 PMID: 38238586
- 8. Liakopoulou A et al.. 2026. ATAD2 mediates chromatin-bound histone chaperone turnover.. Elife 14 PMID: 41557467
