GO:0120325 NuRD complex binding: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0120325 (NuRD complex binding) is a molecular function defined as binding to a NuRD complex, a multi-subunit chromatin-remodeling and histone-deacetylase assembly.
• NuRD complex binding is mediated by short linear motifs, such as the RBBP4-binding motif found in proteins like ZNF512B, which can interact with NuRD subunits independently of the full complex.
• The NuRD complex contains core subunits including HDAC1/2, CHD3/4, MBD2/3, RBBP4/7, MTA1/2/3, and GATAD2A/B, and its binding partners regulate chromatin accessibility and gene expression.
• Dysregulated NuRD complex binding contributes to human diseases including aortic aneurysm and dissection, pediatric glioma, non-small cell lung cancer, and neurodevelopmental disorders with macrocephaly [1,5,7,8].
• Key genes whose protein products bind or are bound by NuRD include HDAC1, ZEB2, CHD2, CHD4, MBD2, RBBP4, and ZNF512B, each with distinct research relevance [1,4,5,6,8].
• CRISPR-based knockout, point-mutation, knock-in, and overexpression models enable causal interrogation of NuRD complex binding in disease and development [1,4,5,6,8].
Description
GO:0120325, NuRD complex binding, is a molecular function term that describes the selective interaction of a protein or other molecule with the nucleosome remodeling and deacetylase (NuRD) complex. The NuRD complex is a large, evolutionarily conserved chromatin-modifying assembly that couples ATP-dependent nucleosome remodeling with histone deacetylation to repress or fine-tune gene expression. Because NuRD complex binding determines which genomic regions and regulatory factors are recruited to this machinery, it is central to developmental gene regulation, cell-fate decisions, and disease-associated transcriptional programs [1,3,7]. Researchers study NuRD complex binding to understand how sequence-specific DNA-binding proteins, chromatin readers, and signaling effectors interface with the NuRD core. For example, the endothelial HDAC1-ZEB2-NuRD complex drives aortic aneurysm and dissection through regulation of protein S-sulfhydration, illustrating how a single binding event can reshape vascular pathophysiology. In pediatric glioma, CHD2 regulates neuron-glioma interactions, linking NuRD-associated chromatin remodeling to tumor microenvironment crosstalk. In non-small cell lung cancer, CHD4 mediates proliferation and migration via the RhoA/ROCK pathway by regulating PHF5A, demonstrating that NuRD subunit binding and downstream effectors influence oncogenic phenotypes. At the molecular level, NuRD complex binding is often mediated by short linear motifs. ZNF512B binds RBBP4 via a variant NuRD interaction motif and aggregates chromatin in a NuRD complex-independent manner, revealing that binding to a NuRD subunit does not always require the intact complex. The topology of chromatin-binding domains in the NuRD deacetylase complex further defines how subunits engage nucleosomes and partner proteins. These findings make GO:0120325 a critical node for interpreting chromatin regulation, developmental disorders, and cancer [2,4,7].
NuRD complex binding At A Glance
| GO ID | GO:0120325 |
|---|---|
| GO term | NuRD complex binding |
| Ontology | molecular_function |
| Synonym | None listed |
| Definition | Binding to a NuRD complex. |
| Major function | Mediates recruitment and physical association of proteins with the NuRD chromatin-remodeling and histone-deacetylase complex. |
| Example binding partners | ZNF512B binds RBBP4 via a variant NuRD interaction motif; HDAC1-ZEB2-NuRD complex forms in endothelial cells. |
| Related disease examples | Aortic aneurysm and dissection; pediatric glioma; non-small cell lung cancer; neurodevelopmental disorders with macrocephaly. |
| Research methods | Co-immunoprecipitation, affinity purification mass spectrometry, chromatin immunoprecipitation, CRISPR knockout and knock-in models [1,4,5,6,8]. |
What Is GO:0120325?
GO:0120325 (NuRD complex binding) is defined by QuickGO as binding to a NuRD complex. In practical terms, it is the molecular function of physically associating with the nucleosome remodeling and deacetylase (NuRD) complex, a multi-subunit assembly that combines histone deacetylation and ATP-dependent chromatin remodeling. This binding can occur through direct contacts with core subunits such as RBBP4, HDAC1/2, or CHD4, and may involve short linear motifs that mediate stable or transient interactions [3,6].
Why Is NuRD complex binding Important in Cell Biology?
NuRD complex binding is important because it determines how the NuRD chromatin-remodeling and deacetylase machinery is targeted to specific genomic loci and regulatory factors, thereby influencing gene expression programs that control development, cell proliferation, and disease [3,7]. Disruption of NuRD complex interactions has been linked to congenital neurodevelopmental disorders with macrocephaly, cancer progression, and vascular pathology, making this molecular function a high-value target for mechanistic and therapeutic research [1,2,5,7,8].
• NuRD complex binding recruits histone deacetylase and chromatin-remodeling activities to specific genomic regions, shaping transcriptional output.
• De novo mutations in developmental disorders frequently affect chromatin-remodeling complexes, including NuRD-associated genes, highlighting the clinical relevance of NuRD complex binding.
• The NuRD complex and macrocephaly-associated neurodevelopmental disorders are directly linked, underscoring the role of NuRD complex binding in brain development.
• Endothelial HDAC1-ZEB2-NuRD complex formation drives aortic aneurysm and dissection through regulation of protein S-sulfhydration.
• CHD2, a NuRD-associated chromatin remodeler, regulates neuron-glioma interactions in pediatric glioma.
• CHD4 mediates proliferation and migration of non-small cell lung cancer via the RhoA/ROCK pathway by regulating PHF5A.
• Targeting redox-sensitive MBD2-NuRD condensates in cancer cells is a potential therapeutic strategy, linking NuRD complex binding to condensate biology.
• ZNF512B binds RBBP4 via a variant NuRD interaction motif and aggregates chromatin in a NuRD complex-independent manner, showing that NuRD subunit binding can have complex-independent functions.
• Understanding NuRD complex binding enables rational design of CRISPR models to test causality of candidate genes in disease [1,4,5,6,8].
• NuRD complex binding is a molecular-function node that connects chromatin topology, gene regulation, and human disease phenotypes [3,7].
GO:0120325 NuRD complex binding: Mechanism, Genes and Research Methods
What Happens During NuRD complex binding?
In simple terms: In simple terms, proteins or regulatory factors attach to the NuRD complex, and this attachment helps decide which genes are turned on or off.
During NuRD complex binding, a partner protein or chromatin-associated factor physically associates with the NuRD complex, which contains histone deacetylase and ATP-dependent remodeling activities. This binding event can recruit NuRD to specific loci, alter chromatin accessibility, and modulate transcription. For example, the endothelial HDAC1-ZEB2-NuRD complex forms and drives aortic aneurysm and dissection through regulation of protein S-sulfhydration, showing that NuRD complex binding can have tissue-specific pathophysiological consequences. In pediatric glioma, CHD2 regulates neuron-glioma interactions, indicating that NuRD-associated binding events influence tumor-microenvironment crosstalk.
Recognition of NuRD subunits by short linear motifs
In simple terms: Some proteins use short, flexible sequence stretches to grab onto NuRD subunits.
NuRD complex binding is often mediated by short linear motifs. ZNF512B binds RBBP4 via a variant NuRD interaction motif and aggregates chromatin in a NuRD complex-independent manner, demonstrating that a single subunit contact can occur outside the context of the intact NuRD complex. The topology of chromatin-binding domains in the NuRD deacetylase complex further defines how subunits engage nucleosomes and partner proteins, which is essential for understanding selectivity and affinity of NuRD complex binding.
Structure and Composition of NuRD complex binding
In simple terms: The NuRD complex is a machine made of many parts, and binding can happen at different parts of the machine.
The NuRD complex is composed of core subunits including HDAC1/2, CHD3/4, MBD2/3, RBBP4/7, MTA1/2/3, and GATAD2A/B, and its chromatin-binding domains determine how it interacts with nucleosomes and partner proteins. Binding partners can contact distinct subunits; for example, ZNF512B binds RBBP4 through a variant NuRD interaction motif. The composition and topology of the NuRD complex therefore dictate which proteins can bind and how binding affects chromatin structure and gene expression.
Molecular Mechanism of NuRD complex binding
In simple terms: At the molecular level, binding is a physical contact between a partner protein and a NuRD subunit, often regulated by chemical modifications or cellular signals.
The molecular mechanism of NuRD complex binding involves direct protein-protein contacts between a partner and NuRD subunits such as RBBP4, HDAC1/2, or CHD4 [3,6]. These contacts can be modulated by post-translational modifications and cellular redox states; for instance, targeting redox-sensitive MBD2-NuRD condensate in cancer cells suggests that NuRD complex binding and condensation are sensitive to redox regulation. In endothelial cells, the HDAC1-ZEB2-NuRD complex regulates protein S-sulfhydration, linking NuRD complex binding to sulfur-based post-translational modifications. CHD4 mediates proliferation and migration of non-small cell lung cancer via the RhoA/ROCK pathway by regulating PHF5A, illustrating downstream signaling consequences of NuRD-associated binding.
Regulation of NuRD complex binding
In simple terms: Cells can tune how tightly or where NuRD binds, depending on signals and metabolic state.
NuRD complex binding is regulated at multiple levels, including subunit availability, post-translational modifications, and cellular redox status [3,4]. Redox-sensitive MBD2-NuRD condensates in cancer cells can be targeted, indicating that condensate formation and binding avidity are regulated by the cellular redox environment. The endothelial HDAC1-ZEB2-NuRD complex responds to pathological cues to drive aortic aneurysm and dissection, showing that binding is not constitutive but context-dependent. In pediatric glioma, CHD2-dependent regulation of neuron-glioma interactions further supports context-specific control of NuRD-associated functions.
Key Genes Involved in GO:0120325 NuRD complex binding
The following genes and their protein products are directly implicated in NuRD complex binding or NuRD-associated functions based on the verified literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| HDAC1 | Histone deacetylase subunit of the NuRD complex; forms HDAC1-ZEB2-NuRD complex in endothelial cells | Drives aortic aneurysm and dissection through regulation of protein S-sulfhydration |
| ZEB2 | Transcription factor that binds HDAC1-NuRD in endothelial cells | Part of the endothelial HDAC1-ZEB2-NuRD complex in aortic disease |
| CHD2 | Chromatin remodeler associated with NuRD-related functions | Regulates neuron-glioma interactions in pediatric glioma |
| CHD4 | ATP-dependent chromatin remodeler and core NuRD subunit | Mediates proliferation and migration of non-small cell lung cancer via RhoA/ROCK and PHF5A |
| MBD2 | Methyl-CpG-binding domain protein that interacts with NuRD | Redox-sensitive MBD2-NuRD condensate is a target in cancer cells |
| RBBP4 | Core NuRD subunit that binds histone chaperone motifs | Binds ZNF512B via a variant NuRD interaction motif |
| ZNF512B | Zinc finger protein that binds RBBP4 | Binds RBBP4 via a variant NuRD interaction motif and aggregates chromatin in a NuRD complex-independent manner |
| MTA1 | Core NuRD subunit | Part of the NuRD complex topology and chromatin-binding domain architecture |
| MTA2 | Core NuRD subunit | Part of the NuRD complex topology and chromatin-binding domain architecture |
| MTA3 | Core NuRD subunit | Part of the NuRD complex topology and chromatin-binding domain architecture |
| GATAD2A | Core NuRD subunit | Part of the NuRD complex composition and chromatin-binding domain architecture |
| GATAD2B | Core NuRD subunit | Part of the NuRD complex composition and chromatin-binding domain architecture |
| HDAC2 | Histone deacetylase subunit of the NuRD complex | Part of the NuRD complex composition and chromatin-binding domain architecture |
| MBD3 | Methyl-CpG-binding domain protein and NuRD subunit | Part of the NuRD complex composition and chromatin-binding domain architecture |
| RBBP7 | Core NuRD subunit | Part of the NuRD complex composition and chromatin-binding domain architecture |
| PHF5A | Downstream effector regulated by CHD4 | Regulated by CHD4 to mediate non-small cell lung cancer proliferation and migration |
How Is NuRD complex binding Regulated?
NuRD complex binding is regulated by subunit availability, post-translational modifications, and cellular redox status [3,4]. Redox-sensitive MBD2-NuRD condensates in cancer cells can be targeted, indicating that condensate formation and binding avidity are modulated by the cellular redox environment. The endothelial HDAC1-ZEB2-NuRD complex responds to pathological cues to drive aortic aneurysm and dissection, showing that binding is context-dependent. In pediatric glioma, CHD2-dependent regulation of neuron-glioma interactions further supports context-specific control of NuRD-associated functions.
NuRD complex binding and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| HDAC1/ZEB2 | Aortic aneurysm and dissection | Endothelial cell knockout or knock-in of HDAC1-ZEB2 binding interface |
| CHD2 | Pediatric glioma | Glioma cell lines with CHD2 knockout or point mutation to test neuron-glioma interactions |
| CHD4 | Non-small cell lung cancer | Lung cancer cell lines with CHD4 knockout or overexpression to assess proliferation and migration |
| MBD2 | Cancer redox biology | Cancer cell lines with MBD2 knockout or point mutation to disrupt redox-sensitive NuRD condensates |
| ZNF512B/RBBP4 | Chromatin aggregation and NuRD-independent functions | Knock-in of variant NuRD interaction motif or RBBP4 binding mutants |
Aortic aneurysm and dissection
The endothelial HDAC1-ZEB2-NuRD complex drives aortic aneurysm and dissection through regulation of protein S-sulfhydration, directly linking NuRD complex binding to vascular disease. This suggests that NuRD complex binding in endothelial cells can be a therapeutic target for aortic wall integrity.
Pediatric glioma
CHD2 regulates neuron-glioma interactions in pediatric glioma, implicating NuRD-associated chromatin remodeling in tumor-microenvironment communication. This highlights NuRD complex binding as a potential node for modulating glioma progression.
Non-small cell lung cancer
CHD4 mediates proliferation and migration of non-small cell lung cancer via the RhoA/ROCK pathway by regulating PHF5A, connecting NuRD complex binding to oncogenic signaling. Targeting CHD4-NuRD interactions may therefore influence lung cancer cell behavior.
Neurodevelopmental disorders with macrocephaly
The NuRD complex is associated with macrocephaly-associated neurodevelopmental disorders, and de novo mutations in developmental disorders frequently affect chromatin-remodeling complexes [2,7]. This underscores the importance of NuRD complex binding in brain development and disease.
From NuRD complex binding-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of NuRD complex binding affect endothelial function? | HDAC1 or ZEB2 knockout endothelial cells |
| Does a point mutation in a NuRD interaction motif disrupt binding? | Point-mutation knock-in of ZNF512B or RBBP4 interface |
| Does NuRD complex binding regulate tumor cell proliferation? | CHD4 knockout or overexpression in non-small cell lung cancer cells |
| Does redox-sensitive NuRD condensate formation require MBD2? | MBD2 knockout or point-mutation cancer cells |
| Does CHD2-dependent NuRD binding influence neuron-glioma interactions? | CHD2 knockout or tagged knock-in in pediatric glioma models |
| Can NuRD complex binding be mapped at endogenous loci? | Tagged knock-in of NuRD subunits for affinity purification and ChIP |
How to Study the NuRD complex binding Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Co-immunoprecipitation | Physical interaction between NuRD subunits and partner proteins | Validate NuRD complex binding in cells [1,6] |
| Affinity purification mass spectrometry | Composition of NuRD complex and associated proteins | Map NuRD interactome and binding interfaces [3,6] |
| ChIP-seq | Genomic localization of NuRD complex binding | Link binding to chromatin state and transcription [3,5] |
| CRISPR knockout | Loss-of-function effect on NuRD complex binding | Test causality in disease models [1,4,5,8] |
| Point-mutation knock-in | Effect of specific residues on binding | Disrupt short linear motifs such as RBBP4-binding motif |
| Overexpression | Gain-of-function effect on NuRD complex binding | Assess oncogenic or developmental phenotypes |
| Proximity labeling | Proteins in close proximity to NuRD subunits | Discover transient or weak NuRD interactors |
| Live-cell imaging | Dynamics of NuRD condensates and binding | Study redox-sensitive MBD2-NuRD condensates |
Affinity purification and mass spectrometry
Affinity purification coupled with mass spectrometry can identify proteins that bind the NuRD complex, including subunits and transient interactors [3,6]. Tagged knock-in of NuRD subunits enables endogenous complex isolation and mapping of binding interfaces.
Co-immunoprecipitation and western blotting
Co-immunoprecipitation of NuRD subunits with candidate binding partners, followed by western blotting, is a standard approach to validate NuRD complex binding [1,6]. This method can test whether point mutations in interaction motifs abolish binding.
Chromatin immunoprecipitation and sequencing
Chromatin immunoprecipitation followed by sequencing (ChIP-seq) can determine where NuRD complex binding occurs across the genome and how it correlates with histone deacetylation and gene expression [3,5].
CRISPR-based functional assays
CRISPR knockout, point-mutation knock-in, and overexpression models allow causal testing of NuRD complex binding in disease phenotypes such as aortic aneurysm, glioma, and lung cancer [1,4,5,6,8].
How CRISPR Can Be Used to Study GO:0120325 NuRD complex binding
Knockout
CRISPR knockout of genes encoding NuRD subunits or binding partners can abolish NuRD complex binding and reveal loss-of-function phenotypes. For example, HDAC1 or ZEB2 knockout can test the role of the endothelial HDAC1-ZEB2-NuRD complex in aortic aneurysm and dissection. CHD4 knockout can assess proliferation and migration in non-small cell lung cancer.
Point Mutation
CRISPR point-mutation knock-in can disrupt specific residues required for NuRD complex binding, such as the variant NuRD interaction motif in ZNF512B that binds RBBP4. This approach distinguishes binding-dependent from binding-independent functions.
Knock-in
CRISPR knock-in of tags or reporters into endogenous NuRD subunit loci enables affinity purification, imaging, and chromatin immunoprecipitation to map NuRD complex binding at native expression levels [3,5].
Overexpression
CRISPR-mediated overexpression of NuRD subunits or binding partners can test gain-of-function effects, such as CHD4 overexpression in lung cancer cells and its impact on proliferation and migration. Overexpression of MBD2 can also probe redox-sensitive NuRD condensate formation.
How EDITGENE Supports NuRD complex binding Research
Researchers studying NuRD complex binding-related genes often need to determine whether a candidate gene is causally involved in chromatin regulation, disease progression, or development. EDITGENE provides CRISPR-based cell model services to interrogate NuRD complex binding with precision and reproducibility.
Contact EDITGENE today to design your custom CRISPR model for NuRD complex binding research.
Frequently Asked Questions About NuRD complex binding
What is GO:0120325 NuRD complex binding?
GO:0120325 is a molecular function term defined as binding to a NuRD complex, a chromatin-remodeling and histone-deacetylase assembly.
What genes are involved in NuRD complex binding?
Genes include HDAC1, ZEB2, CHD2, CHD4, MBD2, RBBP4, and ZNF512B, among others [1,4,5,6,8].
What is the NuRD complex?
The NuRD complex is a multi-subunit assembly containing HDAC1/2, CHD3/4, MBD2/3, RBBP4/7, MTA1/2/3, and GATAD2A/B that couples histone deacetylation with ATP-dependent chromatin remodeling.
How does NuRD complex binding regulate gene expression?
NuRD complex binding recruits deacetylase and remodeling activities to specific loci, altering chromatin accessibility and transcriptional output.
Which diseases are linked to NuRD complex binding?
Aortic aneurysm and dissection, pediatric glioma, non-small cell lung cancer, and neurodevelopmental disorders with macrocephaly have been linked to NuRD complex binding or NuRD-associated genes [1,2,5,7,8].
What is the role of CHD4 in NuRD complex binding?
CHD4 is a core ATP-dependent chromatin remodeler in the NuRD complex and mediates proliferation and migration of non-small cell lung cancer via the RhoA/ROCK pathway by regulating PHF5A.
How can I study NuRD complex binding in the lab?
Common methods include co-immunoprecipitation, affinity purification mass spectrometry, ChIP-seq, and CRISPR knockout or knock-in models [1,3,5,6,8].
What is the ZNF512B-RBBP4 interaction?
ZNF512B binds RBBP4 via a variant NuRD interaction motif and aggregates chromatin in a NuRD complex-independent manner.
Is NuRD complex binding involved in cancer?
Yes, NuRD complex binding is implicated in non-small cell lung cancer through CHD4 and in redox-sensitive MBD2-NuRD condensates in cancer cells [4,8].
What CRISPR models are available for NuRD complex binding research?
Knockout, point-mutation knock-in, tagged knock-in, and overexpression models can be generated for NuRD subunits and binding partners [1,4,5,6,8].
Conclusion
GO:0120325 (NuRD complex binding) defines the physical association of proteins with the NuRD chromatin-remodeling and histone-deacetylase complex, a central node in gene regulation and disease. From endothelial HDAC1-ZEB2-NuRD complexes in aortic disease to CHD2 in pediatric glioma and CHD4 in lung cancer, NuRD complex binding shapes diverse pathological processes [1,5,8]. Understanding its mechanisms, regulation, and disease links requires robust experimental models, and CRISPR-based approaches provide causal insight into this molecular function [4,6,7].
References
- 1. Luo S et al.. 2023. Endothelial HDAC1-ZEB2-NuRD Complex Drives Aortic Aneurysm and Dissection Through Regulation of Protein S-Sulfhydration.. Circulation 147(18):1382-1403 PMID: 36951067
- 2. Deciphering Developmental Disorders Study. 2017. Prevalence and architecture of de novo mutations in developmental disorders.. Nature 542(7642):433-438 PMID: 28135719
- 3. Millard CJ et al.. 2020. The topology of chromatin-binding domains in the NuRD deacetylase complex.. Nucleic Acids Res 48(22):12972-12982 PMID: 33264408
- 4. Wei H et al.. 2025. Targeting redox-sensitive MBD2-NuRD condensate in cancer cells.. Nat Cell Biol 27(5):801-816 PMID: 40307576
- 5. Zhang X et al.. 2024. CHD2 Regulates Neuron-Glioma Interactions in Pediatric Glioma.. Cancer Discov 14(9):1732-1754 PMID: 38767413
- 6. Wunderlich TM et al.. 2024. ZNF512B binds RBBP4 via a variant NuRD interaction motif and aggregates chromatin in a NuRD complex-independent manner.. Nucleic Acids Res 52(21):12831-12849 PMID: 39460621
- 7. Pierson TM et al.. 2019. The NuRD complex and macrocephaly associated neurodevelopmental disorders.. Am J Med Genet C Semin Med Genet 181(4):548-556 PMID: 31737996
- 8. Xu N et al.. 2020. CHD4 mediates proliferation and migration of non-small cell lung cancer via the RhoA/ROCK pathway by regulating PHF5A.. BMC Cancer 20(1):262 PMID: 32228507
