GO:0031011 Ino80 complex: Components, Assembly and Research Methods, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0031011 (Ino80 complex) is a multisubunit, ATP-dependent chromatin-remodeling complex built around the Ino80p/INO80 ATPase that slides and evicts nucleosomes to control DNA accessibility.
• The INO80 complex is conserved from yeast to plants and humans and participates in transcription, DNA replication, and DNA repair.
• INO80 regulates epigenetic inheritance of heterochromatin and higher-order chromatin organization, linking it to genome stability.
• INO80-dependent remodeling of transcriptional regulatory networks underlies progression of heart failure, making it a cardiac disease candidate.
• Chromatin-remodeling factors such as INO80 limit T cell persistence and are emerging immuno-oncology targets identified by genome-wide CRISPR screens.
• Chromatin remodelers, including INO80, are actively pursued as therapeutic targets across cancer and other diseases.
Description
The Ino80 complex (GO:0031011) is a multisubunit protein complex that contains the Ino80p ATPase and exhibits chromatin-remodeling activity. It belongs to the cellular_component aspect of the Gene Ontology and is synonymous with the INO80 chromatin remodeling complex. Chromatin remodelers such as INO80 use the energy of ATP hydrolysis to alter nucleosome positioning and composition, thereby controlling access of transcription factors, replication machinery, and DNA repair factors to the genome. Because of this central role, the Ino80 complex is a key node connecting chromatin structure to gene expression, genome stability, and cell fate. Researchers study GO:0031011 to understand how cells dynamically open and close chromatin during transcription, replication, and repair. The complex is conserved across eukaryotes, including plants, where chromatin remodeling complexes display mechanistic diversity and diverse biological functions. In mammals, INO80 has been implicated in cardiac gene regulation and heart failure progression, and chromatin-remodeling factors including INO80 have been identified as regulators of T cell exhaustion. As chromatin remodelers become therapeutic targets, the Ino80 complex represents both a mechanistic puzzle and a translational opportunity. This article summarizes the definition, composition, molecular mechanism, disease links, and research methods for GO:0031011, with emphasis on how CRISPR-based models can be used to dissect INO80 function in health and disease.
Ino80 complex At A Glance
| GO ID | GO:0031011 |
|---|---|
| GO term | Ino80 complex |
| Ontology | cellular_component |
| Synonym | INO80 chromatin remodeling complex |
| Major function | ATP-dependent chromatin remodeling that regulates nucleosome positioning and DNA accessibility |
| Core subunit | Ino80p/INO80 ATPase |
| Conservation | Conserved across eukaryotes including yeast, plants, and mammals |
| Biological roles | Transcription, DNA replication, DNA repair, and epigenetic inheritance of heterochromatin |
| Disease relevance | Heart failure and T cell exhaustion / immuno-oncology |
What Is GO:0031011?
GO:0031011 (Ino80 complex) is defined as a multisubunit protein complex that contains the Ino80p ATPase and exhibits chromatin-remodeling activity. In practical terms, it is an ATP-dependent machine that binds nucleosomes and changes their position or composition to regulate DNA accessibility.
Why Is Ino80 complex Important in Cell Biology?
The Ino80 complex is important because it sits at the interface of chromatin structure and essentially all DNA-templated processes, including transcription, replication, and repair. By remodeling nucleosomes, INO80 controls which genes can be expressed and how faithfully the genome is duplicated and repaired, making it central to cell identity, stress responses, and genome stability. Its dysfunction or dysregulation has been linked to heart failure and to T cell exhaustion in cancer immunology, and chromatin remodelers as a class are now considered promising therapeutic targets.
• Controls nucleosome positioning and DNA accessibility, thereby regulating transcription, replication, and repair.
• Regulates epigenetic inheritance of heterochromatin, influencing stable gene silencing across cell divisions.
• Is conserved across eukaryotes, enabling mechanistic studies in yeast, plants, and mammalian systems.
• INO80-dependent remodeling of transcriptional networks contributes to heart failure progression.
• Chromatin-remodeling factors including INO80 limit T cell persistence and are relevant to cancer immunotherapy.
• Chromatin remodelers are actively pursued as therapeutic targets in oncology and other diseases.
• Provides a model system for understanding ATP-dependent chromatin remodeling mechanisms.
• Offers opportunities for CRISPR-based functional genomics and drug target validation.
What Happens During Ino80 complex?
Nucleosome recognition and targeting
In simple terms: The Ino80 complex first finds and binds the nucleosome, the DNA-protein spool that packages DNA.
The Ino80 complex is recruited to specific genomic loci through interactions with chromatin marks, transcription factors, and other cofactors, allowing it to act where remodeling is needed. This targeting step determines whether INO80 functions in transcription, replication, or repair contexts.
ATP-dependent nucleosome sliding and eviction
In simple terms: Using ATP as fuel, the complex slides or removes nucleosomes to expose or hide DNA.
The Ino80p ATPase subunit hydrolyzes ATP to drive nucleosome sliding and, in some contexts, histone eviction or exchange, thereby altering DNA accessibility. This remodeling activity is the defining biochemical property of GO:0031011.
Roles in transcription and replication
In simple terms: By moving nucleosomes, INO80 helps turn genes on or off and helps the DNA copying machinery do its job.
The INO80 complex participates in transcriptional regulation and DNA replication, where nucleosome remodeling is required for polymerase access and fork progression. In plants, INO80-containing remodelers contribute to developmental and stress-responsive transcription.
Roles in DNA repair and genome stability
In simple terms: When DNA is damaged, INO80 helps open the chromatin so repair proteins can reach the break.
INO80 functions in DNA repair pathways by remodeling chromatin around damage sites, facilitating repair factor recruitment and genome stability. Loss of INO80 function can impair repair and alter epigenetic inheritance of heterochromatin.
Epigenetic inheritance and higher-order chromatin
In simple terms: INO80 helps pass chromatin states from one cell generation to the next.
The INO80 complex regulates epigenetic inheritance of heterochromatin, influencing how chromatin states are maintained through cell division. This links GO:0031011 to long-term gene silencing and genome organization.
Key Genes Involved in GO:0031011 Ino80 complex
The following genes and proteins represent core subunits and key regulators associated with the Ino80 complex (GO:0031011) and its biological functions.
| Gene | Major Role | Research Relevance |
|---|---|---|
| INO80 | ATPase catalytic subunit of the Ino80 complex | Central to chromatin remodeling, transcription, replication, and repair |
| INO80B | Accessory subunit of the INO80 complex | Contributes to complex integrity and function |
| INO80C | Accessory subunit of the INO80 complex | Supports INO80-mediated remodeling |
| INO80D | Subunit of the INO80 complex | Implicated in transcriptional regulation |
| INO80E | Subunit of the INO80 complex | Contributes to complex assembly and activity |
| ACTR5 | Component of the INO80 complex | Involved in chromatin remodeling |
| ACTR8 | Component of the INO80 complex | Involved in chromatin remodeling |
| YY1 | Transcription factor interacting with INO80 | Links INO80 to transcriptional networks |
| RUVBL1 | AAA+ ATPase associated with INO80 | Supports complex function and genome stability |
| RUVBL2 | AAA+ ATPase associated with INO80 | Supports complex function and genome stability |
| H2A.Z (H2AZ1) | Histone variant exchanged by remodelers | Marker of active chromatin and INO80 activity |
| H2B (H2BC1) | Core histone | Nucleosome substrate for remodeling |
| H3 (H3C1) | Core histone | Nucleosome substrate for remodeling |
| H4 (H4C1) | Core histone | Nucleosome substrate for remodeling |
| TP53 | Tumor suppressor linked to chromatin stress responses | Context for INO80 in genome stability |
| MYC | Oncogenic transcription factor | Chromatin remodeling influences MYC-driven transcription |
| BRCA1 | DNA repair factor | Functional interplay with chromatin remodelers in repair |
How Is Ino80 complex Regulated?
The Ino80 complex is regulated at multiple levels, including subunit composition, post-translational modifications, and recruitment by sequence-specific transcription factors and chromatin marks. Its activity is context-dependent, being directed to transcription, replication, or repair sites by interacting proteins and histone modifications. In plants, INO80-containing remodelers are regulated during development and in response to environmental stress, reflecting diverse regulatory inputs. INO80-dependent remodeling of transcriptional regulatory networks is also dynamically regulated during heart failure progression, indicating disease-context-specific control.
Ino80 complex and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| INO80 | Heart failure | Cardiomyocyte knockout and overexpression models |
| INO80 | T cell exhaustion / cancer immunotherapy | CRISPR knockout in primary T cells |
| INO80 | Genome instability / heterochromatin inheritance | Yeast and mammalian knockout models |
| INO80 | Chromatin remodeling in cancer | Cancer cell line knockout and point-mutation models |
| INO80 | Plant development and stress responses | Plant knockout and knock-in models |
INO80 in heart failure
INO80-dependent remodeling of transcriptional regulatory networks underlies the progression of heart failure, linking GO:0031011 to cardiac gene regulation and disease. This suggests that targeting INO80 activity or its downstream network could modulate maladaptive cardiac transcription.
INO80 and cancer immunology / T cell exhaustion
Genome-wide CRISPR screens of T cell exhaustion identified chromatin remodeling factors, including INO80-related machinery, as limiting T cell persistence. This positions the Ino80 complex as a potential target to improve T cell-based cancer immunotherapy.
Chromatin remodelers as therapeutic targets
Chromatin remodelers, including the INO80 complex, are being explored as therapeutic targets across cancer and other diseases. Their roles in transcription, replication, and repair make them attractive but challenging drug targets.
INO80 and genome stability / epigenetic inheritance
The INO80 complex regulates epigenetic inheritance of heterochromatin and contributes to genome stability, so its dysfunction may contribute to diseases characterized by chromatin instability.
From Ino80 complex-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does INO80 loss alter transcription? | INO80 knockout cell lines with RNA-seq |
| Does INO80 ATPase activity require specific residues? | Point-mutation knock-in of catalytic residues |
| Where does INO80 bind the genome? | Tagged knock-in for ChIP-seq |
| Does INO80 overexpression drive disease phenotypes? | Overexpression cell models |
| Which genes limit T cell persistence? | Genome-wide CRISPR knockout screens |
| How does INO80 regulate heterochromatin inheritance? | Knockout and rescue models |
How to Study the Ino80 complex Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA-seq | Transcriptome changes | INO80 knockout or overexpression effects |
| ChIP-seq | Genome-wide binding sites | INO80 localization and chromatin state |
| ATAC-seq | Chromatin accessibility | Nucleosome remodeling by INO80 |
| CRISPR screens | Gene essentiality and phenotype | Identifying INO80-related regulators |
| Proteomics | Complex composition and interactions | Defining Ino80 complex subunits |
| In vitro remodeling assays | ATP-dependent nucleosome sliding | Mechanistic studies of INO80 |
| Structural biology | 3D architecture of the complex | Understanding INO80 mechanism |
Genome-wide CRISPR screens
Genome-wide CRISPR screens can identify chromatin remodeling factors, including INO80-related genes, that limit T cell persistence and other phenotypes. These screens provide unbiased functional evidence for gene involvement.
Transcriptomics (RNA-seq)
RNA-seq measures how INO80 loss or overexpression reshapes transcriptional networks, as shown in heart failure models. It is a primary readout for INO80-dependent gene regulation.
Chromatin profiling
Chromatin immunoprecipitation and related profiling methods map INO80 binding and nucleosome positioning genome-wide. These approaches define the chromatin-remodeling activity of GO:0031011.
Biochemical and structural assays
In vitro ATPase and nucleosome-remodeling assays, together with structural studies, define the molecular mechanism of the Ino80 complex. Such assays are essential for mechanistic dissection.
How CRISPR Can Be Used to Study GO:0031011 Ino80 complex
Knockout
CRISPR knockout of INO80 or its subunits can reveal loss-of-function phenotypes in transcription, replication, repair, and disease models. Knockout cell lines are foundational for assigning causality to GO:0031011.
Point Mutation
Point-mutation knock-in of catalytic residues in the INO80 ATPase can separate ATPase activity from scaffolding functions. Such models are valuable for mechanistic dissection of chromatin remodeling.
Knock-in
Tagged knock-in of INO80 enables endogenous localization and interaction studies without overexpression artifacts. This supports genome-wide mapping of INO80 binding and complex assembly.
Overexpression
Overexpression models can test whether increased INO80 activity drives disease-relevant transcriptional programs, as in heart failure. They complement loss-of-function approaches.
How EDITGENE Supports Ino80 complex Research
Researchers studying Ino80 complex-related genes often need to determine whether a candidate gene is causally involved in chromatin remodeling, transcription, or disease phenotypes. Rigorous causal testing requires well-controlled genetic models, including knockout, point-mutation, knock-in, and overexpression cell lines, as well as functional genomics screens.
Contact EDITGENE today to design your custom CRISPR model for Ino80 complex research.
Frequently Asked Questions About Ino80 complex
What is the Ino80 complex (GO:0031011)?
The Ino80 complex is a multisubunit protein complex that contains the Ino80p ATPase and exhibits chromatin-remodeling activity.
What genes are involved in the Ino80 complex?
Core components include INO80, INO80B, INO80C, INO80D, INO80E, ACTR5, ACTR8, RUVBL1, and RUVBL2.
What does the Ino80 complex do?
It uses ATP to slide or evict nucleosomes, regulating transcription, DNA replication, and DNA repair.
Where is the Ino80 complex found?
It is conserved across eukaryotes, including yeast, plants, and mammals.
How is the Ino80 complex linked to disease?
INO80-dependent remodeling contributes to heart failure progression and chromatin remodeling factors limit T cell persistence in cancer immunology.
Is the Ino80 complex a drug target?
Chromatin remodelers, including INO80, are being explored as therapeutic targets across diseases.
How do researchers study the Ino80 complex?
Common methods include CRISPR screens, RNA-seq, ChIP-seq, ATAC-seq, proteomics, and in vitro remodeling assays.
What is the difference between INO80 and other remodelers?
INO80 is defined by the Ino80p ATPase and is distinct in subunit composition and function from other remodeling complexes.
Can CRISPR knockout be used to study INO80?
Yes, CRISPR knockout of INO80 and its subunits is widely used to test loss-of-function phenotypes.
What models are available for INO80 research?
Knockout, point-mutation, knock-in, tagged knock-in, and overexpression cell models, plus CRISPR library screening, are available.
Conclusion
The Ino80 complex (GO:0031011) is a conserved, ATP-dependent chromatin-remodeling machine that controls DNA accessibility for transcription, replication, and repair. Its roles in epigenetic inheritance, heart failure, and T cell exhaustion make it a compelling target for mechanistic and translational research. CRISPR-based knockout, point-mutation, knock-in, and overexpression models, combined with functional genomics and bioinformatics, provide the tools needed to dissect INO80 biology and its disease relevance.
References
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- 2. Ren Z et al.. 2024. INO80-Dependent Remodeling of Transcriptional Regulatory Network Underlies the Progression of Heart Failure.. Circulation 149(14):1121-1138 PMID: 38152931
- 3. Jain R et al.. 2024. Epigenetics.. Adv Exp Med Biol 1441:341-364 PMID: 38884720
- 4. Malone HA et al.. 2024. Chromatin remodellers as therapeutic targets.. Nat Rev Drug Discov 23(9):661-681 PMID: 39014081
- 5. Reyes AA et al.. 2021. Structure and Function of Chromatin Remodelers.. J Mol Biol 433(14):166929 PMID: 33711345
- 6. Huang Y et al.. 2025. Chromatin remodeling in plants: Complex composition, mechanistic diversity, and biological functions.. Mol Plant 18(9):1436-1457 PMID: 40808254
- 7. Shan CM et al.. 2020. The INO80 Complex Regulates Epigenetic Inheritance of Heterochromatin.. Cell Rep 33(13):108561 PMID: 33378674
- 8. Conaway RC et al.. 2009. The INO80 chromatin remodeling complex in transcription, replication and repair.. Trends Biochem Sci 34(2):71-7 PMID: 19062292
