GO:0110016 B-WICH complex: Components, Assembly and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0110016 defines the B-WICH complex, a nucleolar chromatin-remodeling machine that positively regulates histone H3 acetylation, especially H3K9, by recruiting histone acetyltransferases to rDNA gene regions.
• The B-WICH complex assembles on RNA Polymerase I (Pol I) and possibly Pol III promoter and coding regions during early G1 phase and activates post-initiation phases of Pol I transcription.
• In mammals, B-WICH contains the WICH complex core of BAZ1B and SMARCA5, additional protein subunits, and possibly rRNAs.
• B-WICH also regulates RNA polymerase III transcription by promoting Max-dependent c-Myc binding.
• The complex responds to glucose availability and coordinates ribosomal transcription with metabolic state through interplay with NuRD.
• B-WICH is linked to nuclear myosin 1, viral replication, and broader roles in transcription, repair, and replication.
Description
The B-WICH complex (GO:0110016) is a chromatin-remodeling assembly that positively regulates histone H3 acetylation, particularly at H3K9, by recruiting histone acetyltransferases to ribosomal DNA (rDNA) gene regions. It is located in the nucleolus, where it assembles on RNA Polymerase I (Pol I) and possibly on RNA Polymerase III (Pol III) promoter and coding regions during early G1 phase, activating post-initiation phases of Pol I transcription. The complex may also activate RNA Polymerase II (Pol II) gene transcription. In mammals, B-WICH contains the WICH complex core of BAZ1B and SMARCA5, additional protein subunits, and possibly rRNAs. Although it contains several catalytic subunits, it is not clear which functions are carried out by the complex itself.
B-WICH complex At A Glance
| GO ID | GO:0110016 |
|---|---|
| GO term | B-WICH complex |
| Ontology | cellular_component |
| Synonym | None |
| Major function | Chromatin remodeling that positively regulates histone H3 acetylation, especially H3K9, by recruiting histone acetyltransferases to rDNA gene regions |
| Location | Nucleolus, assembling on RNA Polymerase I and possibly RNA Polymerase III promoter and coding regions |
| Cell cycle timing | Assembles during early G1 phase and activates post-initiation phases of Pol I transcription |
| Core subunits | BAZ1B and SMARCA5 (WICH complex core), plus additional protein subunits and possibly rRNAs |
| Additional roles | May activate RNA Polymerase II gene transcription; regulates Pol III transcription via Max-dependent c-Myc binding |
What Is GO:0110016?
GO:0110016 describes the B-WICH complex as a chromatin-remodeling complex that positively regulates histone H3 acetylation, in particular H3K9, by recruiting histone acetyltransferases to rDNA gene regions. It is located in the nucleolus where it assembles on RNA Polymerase I (Pol I) and possibly on RNA Polymerase III (Pol III) promoter and coding regions during early G1 phase and activates the post-initiation phases of Pol I transcription. It may also activate RNA Polymerase II (Pol II) gene transcription. In mammals, B-WICH contains the WICH complex core of BAZ1B and SMARCA5, additional protein subunits and possibly rRNAs. Although it contains several catalytic subunits it is not clear which functions are carried out by the complex itself.
Why Is B-WICH complex Important in Cell Biology?
The B-WICH complex is important because it couples chromatin remodeling to ribosomal RNA synthesis, a rate-limiting step for ribosome biogenesis and cell growth. By recruiting histone acetyltransferases to rDNA, it establishes an active chromatin state that enables efficient Pol I transcription. Its regulation by glucose availability and interplay with NuRD highlights its role in metabolic sensing and transcriptional coordination. Furthermore, B-WICH influences Pol III transcription through c-Myc, linking it to oncogenic pathways and viral replication. Understanding B-WICH provides insights into nucleolar function, cell cycle progression, and diseases such as cancer and ribosomopathies.
• Regulates ribosomal RNA synthesis, a fundamental process for ribosome biogenesis and protein production.
• Recruits histone acetyltransferases to rDNA, promoting H3K9 acetylation and active chromatin.
• Coordinates Pol I transcription with cell cycle progression during early G1 phase.
• Modulates Pol III transcription via Max-dependent c-Myc binding, impacting tRNA and 5S rRNA synthesis.
• Responds to glucose availability, linking metabolic state to ribosomal transcription.
• Interacts with NuRD to balance chromatin remodeling and transcriptional output.
• Involved in viral replication through association with papillomavirus E2 protein and nuclear myosin 1.
• Implicated in cancer biology via BAZ1B and c-Myc pathways.
• Potential roles in ribosomopathies and developmental disorders due to BAZ1B mutations.
• Provides a model for studying chromatin remodeling complex assembly and function.
What Happens During B-WICH complex?
Assembly on rDNA and Pol I Machinery
In simple terms: The B-WICH complex builds itself on ribosomal DNA and the enzyme that reads it.
During early G1 phase, the B-WICH complex assembles in the nucleolus on RNA Polymerase I (Pol I) promoter and coding regions, and possibly on Pol III regions. This assembly is essential for its chromatin-remodeling activity and subsequent recruitment of histone acetyltransferases.
Histone Acetylation and Chromatin Remodeling
In simple terms: B-WICH opens up tightly packed DNA by adding acetyl marks to histones.
B-WICH positively regulates histone H3 acetylation, particularly H3K9, by recruiting histone acetyltransferases to rDNA gene regions. This acetylation neutralizes positive charges on histones, loosening chromatin and facilitating transcription factor access.
Activation of Pol I Transcription
In simple terms: B-WICH helps the RNA polymerase I enzyme start and continue reading ribosomal RNA genes.
The complex activates post-initiation phases of Pol I transcription, enhancing rRNA synthesis. It may also activate RNA Polymerase II gene transcription, though this role is less defined.
Regulation of Pol III Transcription
In simple terms: B-WICH also controls another polymerase that makes small RNAs.
B-WICH regulates RNA polymerase III transcription by promoting Max-dependent c-Myc binding. This links B-WICH to the synthesis of tRNAs and 5S rRNA, which are required for translation.
Response to Glucose and Metabolic Cues
In simple terms: B-WICH adjusts ribosomal RNA production based on sugar availability.
The chromatin-remodeling complexes B-WICH and NuRD regulate ribosomal transcription in response to glucose. This ensures that ribosome production matches cellular energy status.
Key Genes Involved in GO:0110016 B-WICH complex
The following genes and proteins are key components or interactors of the B-WICH complex, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| BAZ1B | Core subunit of WICH complex; bromodomain-containing protein that binds acetylated histones | Mutations linked to Williams-Beuren syndrome; role in transcription, repair, and replication |
| SMARCA5 | Core ATPase subunit of WICH complex; chromatin remodeling | Essential for nucleosome sliding and transcriptional regulation |
| MYO1C | Nuclear myosin 1; interacts with B-WICH and Pol I | Links chromatin remodeling to nuclear actin and transcription |
| c-Myc | Transcription factor recruited by B-WICH to Pol III genes | Oncogene; regulates Pol III transcription and cell growth |
| MAX | Partner of c-Myc; required for B-WICH-mediated Pol III regulation | Involved in transcriptional activation and repression |
| SIRT7 | NAD+-dependent deacetylase; interacts with Pol I and rDNA chromatin | Regulates ribosomal RNA synthesis and stress responses |
| NuRD complex | Chromatin remodeling complex that antagonizes B-WICH | Regulates ribosomal transcription in response to glucose |
| RNA Polymerase I | Enzyme that transcribes rRNA genes | Target of B-WICH activation |
| RNA Polymerase III | Enzyme that transcribes tRNA and 5S rRNA genes | Regulated by B-WICH via c-Myc |
| RNA Polymerase II | Enzyme that transcribes mRNA genes | May be activated by B-WICH |
| Histone H3 | Substrate for acetylation at K9 | Acetylation marks active chromatin |
| Histone acetyltransferases | Enzymes recruited by B-WICH to acetylate H3 | Effectors of chromatin opening |
| Papillomavirus E2 | Viral protein that associates with nuclear myosin 1 | Influences viral replication via B-WICH components |
| WSTF (BAZ1B) | Multifunctional protein in transcription, repair, and replication | Also known as BAZ1B; key to B-WICH function |
| rRNA | Possible component of B-WICH | May contribute to complex structure or regulation |
| Actin | Nuclear actin involved in transcription | Interacts with nuclear myosin 1 |
| SIRT7 | Deacetylase that regulates Pol I | Potential antagonist of B-WICH acetylation |
| Glucose | Metabolic signal regulating B-WICH and NuRD | Links nutrient status to ribosomal transcription |
How Is B-WICH complex Regulated?
The B-WICH complex is regulated by cell cycle timing, assembling during early G1 phase to activate Pol I transcription. It responds to glucose availability, with B-WICH and NuRD coordinating ribosomal transcription based on metabolic state. Additionally, B-WICH function in Pol III transcription is mediated by Max-dependent c-Myc binding, linking it to growth factor signaling. Sirtuin 7 (SIRT7) may also modulate rDNA chromatin and Pol I activity, potentially counterbalancing B-WICH-mediated acetylation.
B-WICH complex and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| BAZ1B | Williams-Beuren syndrome; cancer | Knockout or point-mutation cell lines; patient-derived iPSCs |
| SMARCA5 | Cancer; developmental disorders | Knockout and rescue experiments in cancer cell lines |
| c-Myc | Cancer; oncogenesis | Overexpression and knockout models in lymphoma or carcinoma lines |
| SIRT7 | Cancer; metabolic stress | Knockout and overexpression in hepatocytes or cancer cells |
| MYO1C | Viral replication; transcription | Knockout in epithelial cells; viral infection models |
Cancer
B-WICH components are implicated in cancer through their roles in ribosomal RNA synthesis and c-Myc regulation. BAZ1B (WSTF) is a multifunctional protein involved in transcription, repair, and replication, and its dysregulation may contribute to oncogenesis. The complex's regulation of Pol III transcription via c-Myc links it to cell growth and proliferation pathways commonly activated in cancer.
Williams-Beuren Syndrome
BAZ1B, a core subunit of B-WICH, is located in the Williams-Beuren syndrome critical region. Haploinsufficiency of BAZ1B is associated with the neurodevelopmental and craniofacial features of this disorder, highlighting the importance of B-WICH in development.
Ribosomopathies
Given its central role in ribosomal RNA transcription, disruption of B-WICH function could contribute to ribosomopathies, a group of diseases caused by defective ribosome biogenesis. The complex's response to glucose and interplay with NuRD further suggests that metabolic stress may exacerbate such conditions.
Viral Infections
B-WICH components interact with viral proteins such as papillomavirus E2, influencing viral replication. Nuclear myosin 1, a B-WICH interactor, associates with E2 and affects viral genome maintenance, suggesting a role for B-WICH in viral pathogenesis.
From B-WICH complex-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does BAZ1B loss affect rDNA transcription? | BAZ1B knockout cell line (e.g., HEK293T) with rRNA quantification |
| How does SMARCA5 ATPase activity contribute to B-WICH function? | SMARCA5 point-mutation (ATPase-dead) knock-in |
| What is the role of H3K9 acetylation in B-WICH recruitment? | Histone H3K9A or H3K9R point-mutation knock-in |
| Can B-WICH components be tracked in live cells? | Endogenous BAZ1B or SMARCA5 tagged with fluorescent protein via knock-in |
| Does B-WICH overexpression alter Pol III output? | Doxycycline-inducible overexpression of BAZ1B and SMARCA5 |
| Which genes are regulated by B-WICH under glucose starvation? | CRISPR knockout of BAZ1B followed by RNA-seq and Ribo-seq |
How to Study the B-WICH complex Process
| Method | What It Measures | Typical Application |
|---|---|---|
| ChIP-seq | Genome-wide binding of B-WICH subunits and histone marks | Mapping B-WICH on rDNA and Pol III genes |
| RNA-seq | Transcript levels of rRNA, tRNA, and mRNAs | Assessing transcriptional changes after knockout |
| Ribo-seq | Translation efficiency and ribosome occupancy | Linking B-WICH to protein synthesis |
| Co-IP / Mass Spectrometry | Protein-protein interactions and complex composition | Identifying novel B-WICH subunits |
| Fluorescence microscopy | Subcellular localization and dynamics | Visualizing B-WICH in nucleoli |
| ATAC-seq | Chromatin accessibility | Measuring chromatin opening at rDNA |
| qRT-PCR | Specific RNA levels | Validating rRNA and tRNA changes |
| Western blot | Protein expression and acetylation status | Checking H3K9ac and subunit levels |
Chromatin Immunoprecipitation (ChIP)
ChIP with antibodies against BAZ1B, SMARCA5, or acetylated H3K9 can map B-WICH binding sites on rDNA and Pol I/III promoters. This method reveals dynamic assembly during cell cycle and glucose response.
RNA Sequencing (RNA-seq) and Ribo-seq
RNA-seq measures changes in rRNA, tRNA, and mRNA levels upon B-WICH perturbation. Ribo-seq provides a snapshot of translation efficiency, linking B-WICH function to protein synthesis.
Proteomics and Co-Immunoprecipitation
Affinity purification of BAZ1B or SMARCA5 followed by mass spectrometry identifies additional B-WICH subunits and interactors, including nuclear myosin 1 and c-Myc.
Live-Cell Imaging
Fluorescent tagging of B-WICH components enables real-time visualization of complex assembly in nucleoli and its dynamics during the cell cycle.
How CRISPR Can Be Used to Study GO:0110016 B-WICH complex
Knockout
CRISPR knockout of BAZ1B or SMARCA5 disrupts B-WICH complex formation, leading to reduced H3K9 acetylation at rDNA and decreased Pol I transcription. Knockout cell lines are valuable for studying the complex's role in cell cycle progression and glucose response.
Point Mutation
Point mutations in the ATPase domain of SMARCA5 or the bromodomain of BAZ1B can dissect specific functions. For example, an ATPase-dead SMARCA5 knock-in abolishes chromatin remodeling while preserving complex assembly.
Knock-in
Knock-in of epitope tags (e.g., FLAG, HA) or fluorescent proteins into endogenous BAZ1B or SMARCA5 loci enables affinity purification and live-cell imaging of the B-WICH complex without overexpression artifacts.
Overexpression
Doxycycline-inducible overexpression of BAZ1B and SMARCA5 allows controlled upregulation of B-WICH activity, useful for studying its effects on Pol I and Pol III transcription and cell growth.
How EDITGENE Supports B-WICH complex Research
Researchers studying B-WICH complex-related genes often need to determine whether a candidate gene is causally involved in chromatin remodeling, ribosomal transcription, or disease. EDITGENE provides comprehensive CRISPR-based services to generate precisely engineered cell models, enabling functional validation of B-WICH components and their regulators.
Contact EDITGENE today to design your custom CRISPR model for B-WICH complex research.
Frequently Asked Questions About B-WICH complex
What is the B-WICH complex?
The B-WICH complex (GO:0110016) is a nucleolar chromatin-remodeling complex that positively regulates histone H3 acetylation, especially H3K9, by recruiting histone acetyltransferases to rDNA gene regions.
What genes are involved in the B-WICH complex?
Key genes include BAZ1B and SMARCA5, which form the WICH core, along with interactors such as MYO1C, c-Myc, and MAX.
Where is the B-WICH complex located?
It is located in the nucleolus, where it assembles on RNA Polymerase I and possibly RNA Polymerase III promoter and coding regions.
What is the function of BAZ1B in B-WICH?
BAZ1B is a core subunit that binds acetylated histones and contributes to chromatin remodeling, transcription, repair, and replication.
How does B-WICH regulate RNA polymerase I transcription?
B-WICH recruits histone acetyltransferases to rDNA, promoting H3K9 acetylation and activating post-initiation phases of Pol I transcription.
Does B-WICH regulate RNA polymerase III?
Yes, B-WICH regulates Pol III transcription by promoting Max-dependent c-Myc binding.
What diseases are associated with B-WICH complex mutations?
Mutations in BAZ1B are linked to Williams-Beuren syndrome, and B-WICH components are implicated in cancer and ribosomopathies.
How is the B-WICH complex regulated by glucose?
B-WICH and NuRD coordinate ribosomal transcription in response to glucose availability, ensuring ribosome production matches metabolic state.
What research methods are used to study B-WICH?
Common methods include ChIP-seq, RNA-seq, Ribo-seq, co-immunoprecipitation, and live-cell imaging.
Can CRISPR be used to study B-WICH complex genes?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models enable precise functional dissection of B-WICH components.
Conclusion
The B-WICH complex (GO:0110016) is a critical nucleolar chromatin-remodeling machine that links histone acetylation to ribosomal RNA synthesis. Its core subunits BAZ1B and SMARCA5, along with interactors like c-Myc and nuclear myosin 1, position it at the intersection of transcription, cell cycle, and metabolism. Dysregulation of B-WICH components is associated with developmental disorders and cancer, making it a compelling target for further research. CRISPR-based models will continue to illuminate its mechanistic roles and therapeutic potential.
References
- 1. Sadeghifar F et al.. 2015. The B-WICH chromatin-remodelling complex regulates RNA polymerase III transcription by promoting Max-dependent c-Myc binding.. Nucleic Acids Res 43(9):4477-90 PMID: 25883140
- 2. Vintermist A et al.. 2011. The chromatin remodelling complex B-WICH changes the chromatin structure and recruits histone acetyl-transferases to active rRNA genes.. PLoS One 6(4):e19184 PMID: 21559432
- 3. Sharif SB et al.. 2021. BAZ1B the Protean Protein.. Genes (Basel) 12(10) PMID: 34680936
- 4. Rolicka A et al.. 2020. The chromatin-remodeling complexes B-WICH and NuRD regulate ribosomal transcription in response to glucose.. FASEB J 34(8):10818-10834 PMID: 32598531
- 5. Percipalle P et al.. 2006. Chromatin remodelling and transcription: be-WICHed by nuclear myosin 1.. Curr Opin Cell Biol 18(3):267-74 PMID: 16574391
- 6. Barnett C et al.. 2011. WSTF does it all: a multifunctional protein in transcription, repair, and replication.. Biochem Cell Biol 89(1):12-23 PMID: 21326359
- 7. Sankovski E et al.. 2018. Nuclear myosin 1 associates with papillomavirus E2 regulatory protein and influences viral replication.. Virology 514:142-155 PMID: 29179037
- 8. Kiran S et al.. 2015. Sirtuin 7 in cell proliferation, stress and disease: Rise of the Seventh Sirtuin!. Cell Signal 27(3):673-82 PMID: 25435428
