NAP1L1 Human
Description
Functional Roles
NAP1L1 serves as a histone chaperone with diverse roles:
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Chromatin Assembly: Facilitates nucleosome formation by shuttling histones H2A-H2B into the nucleus .
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DNA Repair: Enhances ERCC6-mediated transcription-coupled repair and RAD51/RAD54-dependent homologous recombination .
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Cell Cycle Regulation: Promotes G2/M phase transition via CDK1 and β-catenin activation .
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Disease Pathways:
3.1. Cancer Biomarker
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Prognostic Value: High NAP1L1 expression correlates with poor survival in HCC (HR = 1.67, p < 0.001) and colorectal cancer .
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Mechanistic Insights:
3.2. Non-Oncological Roles
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Platelet Function: Binds DLAT (PDC-E2) to modulate mitochondrial PDH activity, impacting thrombopoiesis .
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Neurogenesis: Regulates neural progenitor proliferation via RASSF10 promoter methylation .
Research Applications
NAP1L1 is widely used in:
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Chromatin Assembly Assays: Validated for histone deposition and nucleosome remodeling .
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Protein Interaction Studies: Identified partners include HDGF, c-Jun, and YAP1 .
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Disease Modeling:
Key Research Findings
Future Directions
Current research gaps include:
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Mechanistic Depth: How NAP1L1 precisely regulates immune cells (e.g., macrophages) in HCC.
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Therapeutic Targeting: Small-molecule inhibitors to disrupt NAP1L1-YAP1 or NAP1L1-UBR4 interactions.
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Clinical Validation: Multicenter studies to confirm its prognostic utility across cancer types.
Product Specs
Q&A
Experimental Design for Studying NAP1L1 Function
Q: How can I design experiments to study the role of NAP1L1 in nucleosome assembly and DNA repair mechanisms? A: To study NAP1L1's role, you can use a combination of biochemical assays and cell-based experiments. For example, co-immunoprecipitation can help identify interactions with histones and other DNA repair proteins. Additionally, using siRNA or CRISPR to knockdown NAP1L1 in cells can reveal its impact on nucleosome assembly and DNA repair processes like homologous recombination and nucleotide excision repair .
Data Analysis for Contradictory Results
Q: How do I analyze contradictory data regarding NAP1L1's involvement in different cellular processes? A: When analyzing contradictory data, consider the experimental conditions, cell types used, and the specific assays performed. For instance, differences in NAP1L1's role in DNA repair versus neurogenesis might stem from variations in cellular context or experimental design. Use meta-analysis techniques to synthesize findings across studies and identify potential biases or confounding factors .
Advanced Research Questions on NAP1L1's Mechanism
Q: What advanced techniques can I use to investigate the molecular mechanisms by which NAP1L1 influences nucleosome remodeling and chromatin dynamics? A: Techniques such as single-molecule fluorescence microscopy and chromatin immunoprecipitation sequencing (ChIP-seq) can provide insights into NAP1L1's role in nucleosome remodeling and chromatin structure. These methods allow for the observation of real-time interactions between NAP1L1 and chromatin components at high resolution .
Methodological Considerations for NAP1L1 Expression Studies
Q: How can I ensure accurate measurement of NAP1L1 expression levels in different tissues or cell types? A: For accurate measurement of NAP1L1 expression, use quantitative real-time PCR (qRT-PCR) with validated primers and normalize against appropriate housekeeping genes. Additionally, consider using Western blotting to confirm protein levels, as mRNA levels may not always correlate with protein expression due to post-transcriptional regulation .
NAP1L1 in Disease Models
Q: What approaches can be used to study NAP1L1's potential role in disease models, such as cancer or neurodevelopmental disorders? A: To study NAP1L1's role in disease models, use genetically modified animal models or cell lines where NAP1L1 expression is altered. Analyze phenotypic changes and molecular alterations in these models using techniques like RNA sequencing and ChIP-seq to understand how NAP1L1 contributes to disease pathology .
Interpretation of NAP1L1's Role in Neurogenesis
Q: How can I interpret the role of NAP1L1 in regulating neurogenesis, particularly its impact on neural progenitor proliferation and differentiation? A: Interpretation of NAP1L1's role in neurogenesis involves analyzing its effects on neural progenitor cell proliferation and differentiation markers. Use techniques like immunofluorescence staining for neural markers and BrdU incorporation assays to assess cell proliferation. Additionally, examine the expression of genes involved in neurogenesis pathways to understand how NAP1L1 modulates these processes .
NAP1L1 and Chromatin Remodeling
Q: What methods can be employed to study how NAP1L1 interacts with chromatin remodeling complexes and influences nucleosome dynamics? A: To study NAP1L1's interaction with chromatin remodeling complexes, use biochemical assays such as co-immunoprecipitation and in vitro nucleosome remodeling assays. Techniques like single-molecule FRET can provide real-time insights into how NAP1L1 affects nucleosome movement and stability .
NAP1L1 as a Biomarker
Q: How can NAP1L1 be evaluated as a potential biomarker for diseases like colorectal cancer? A: To evaluate NAP1L1 as a biomarker, conduct studies comparing its expression levels in diseased versus healthy tissues using techniques like qRT-PCR and Western blotting. Analyze the correlation between NAP1L1 expression and disease progression or prognosis. Additionally, consider using liquid biopsy techniques to assess NAP1L1 levels in circulating biomarkers .
Advanced Techniques for Studying NAP1L1 Interactions
Q: What advanced biophysical techniques can be used to study the interactions between NAP1L1 and histones or other chromatin-associated proteins? A: Techniques such as surface plasmon resonance (SPR), isothermal titration calorimetry (ITC), and nuclear magnetic resonance (NMR) spectroscopy can provide detailed insights into the binding affinities and structural interactions between NAP1L1 and its protein partners .
Data Integration and Bioinformatics Analysis
Q: How can I integrate and analyze large-scale genomic and proteomic data related to NAP1L1 to identify novel regulatory pathways? A: Use bioinformatics tools like pathway analysis software (e.g., Metascape) to integrate genomic and proteomic data. Perform gene set enrichment analysis (GSEA) to identify pathways enriched with NAP1L1-interacting genes. Additionally, construct regulatory networks using tools like Cytoscape to visualize interactions between NAP1L1 and other proteins or genes .
Table: NAP1L1 Protein Characteristics
| Characteristic | Description |
|---|---|
| Source | Expressed in Escherichia coli |
| Purity | >90% |
| Length | 1-388 amino acids (full-length) |
| Molecular Mass | Approximately 47.2 kDa |
| Function | Histone chaperone involved in nucleosome assembly and DNA repair |
Figure: NAP1L1's Role in Nucleosome Remodeling
To visualize NAP1L1's role in nucleosome remodeling, consider using diagrams that illustrate how it interacts with chromatin remodeling complexes and histones to facilitate nucleosome assembly and disassembly. This can help in understanding its impact on chromatin dynamics and gene expression.
Product Science Overview
NAP1L1 functions primarily as a histone chaperone, facilitating the proper assembly and disassembly of nucleosomes. This activity is essential for maintaining chromatin structure and regulating gene expression. Some of the key functions of NAP1L1 include:
- Nucleosome Assembly: NAP1L1 assists in the deposition of histones H2A and H2B onto DNA, forming nucleosomes .
- DNA Repair: It enhances chromatin remodeling, which is crucial for DNA repair mechanisms such as transcription-coupled nucleotide excision repair and homologous recombination .
- Cell Proliferation: NAP1L1 is involved in modulating chromatin formation, thereby contributing to the regulation of cell proliferation .
The activity of NAP1L1 is regulated through various post-translational modifications, including phosphorylation and acetylation. These modifications influence its interaction with histones and other chromatin-associated proteins, thereby modulating its function in nucleosome assembly and chromatin remodeling .
Mutations or dysregulation of NAP1L1 have been associated with several diseases, including certain cancers and viral infections. For instance, NAP1L1 has been implicated in the reactivation of Epstein-Barr virus in epithelial cells . Additionally, its role in cell proliferation and DNA repair makes it a potential target for therapeutic interventions in cancer treatment .
