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Cancer-related gene regulation
Research Guide
What is Cancer-related gene regulation?
Cancer-related gene regulation is the control of gene expression in cancer cells through posttranslational modifications such as protein arginine methylation by PRMT1 and PRMT5, histone methylation, and epigenetic mechanisms that influence transcriptional regulation, chromatin access, and cell proliferation.
This field examines protein arginine methylation, particularly by PRMT1 and PRMT5 in mammals, and its roles in histone methylation, transcriptional regulation, and epigenetic control with implications for cancer. A total of 39,285 papers address these processes. Distinct histone amino-terminal modifications regulate DNA access, as shown in foundational studies on the histone code.
Topic Hierarchy
Research Sub-Topics
PRMT5 in Cancer Epigenetics
This sub-topic examines the role of PRMT5-mediated symmetric dimethylarginine modifications on histones and non-histone proteins in regulating gene expression in cancer cells. Researchers investigate PRMT5 inhibitors and their therapeutic potential in oncology.
PRMT1 Transcriptional Regulation
This sub-topic focuses on PRMT1 asymmetric dimethylarginine activity in modulating transcription factors and co-activators to control gene transcription in mammalian cells. Studies explore its interplay with RNA polymerase II and implications for cell proliferation.
Histone Arginine Methylation in Gene Regulation
Researchers study site-specific arginine methylation on histones H3 and H4 by PRMTs and its effects on chromatin structure and transcriptional activation or repression. This includes mapping methylation patterns via mass spectrometry and ChIP-seq.
PRMTs in DNA Damage Response
This sub-topic investigates how PRMT1 and PRMT5 methylate DNA repair proteins like MRE11 and 53BP1 to regulate homologous recombination and non-homologous end joining in cancer cells. Studies link these modifications to genome stability and chemotherapy resistance.
Non-Histone Protein Arginine Methylation in Signaling
Focuses on arginine methylation of signaling proteins such as RAF, AKT, and splice factors by PRMTs, affecting pathways like MAPK and PI3K in cancer proliferation. Researchers use proteomics to identify novel substrates and functional impacts.
Why It Matters
Cancer-related gene regulation impacts tumor suppressor gene silencing and cell proliferation through epigenetic changes like histone and DNA methylation. For instance, 'Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands' by Herman et al. (1996) introduced MSP, a method essential for mapping CpG island methylation patterns in cancer, enabling detection of tumor suppressor silencing with 5642 citations. Papers like 'Translating the Histone Code' by Jenuwein and Allis (2001) with 9604 citations reveal how chromatin modifications control gene access, directly linking to cancer progression. 'Regulation of Ferroptotic Cancer Cell Death by GPX4' by Yang et al. (2014) with 7013 citations demonstrates GPX4's role in preventing ferroptotic death in cancer cells, highlighting regulatory pathways for targeted therapies.
Reading Guide
Where to Start
'Translating the Histone Code' by Jenuwein and Allis (2001), as it provides the foundational concept of histone modifications regulating chromatin and gene access, essential for understanding cancer epigenetics.
Key Papers Explained
'Translating the Histone Code' by Jenuwein and Allis (2001) establishes the histone modification code, built upon by Strahl and Allis (2000) in 'The language of covalent histone modifications' detailing covalent marks' specificity. Barski et al. (2007) in 'High-Resolution Profiling of Histone Methylations in the Human Genome' applies this genomically, while Bannister and Kouzarides (2011) in 'Regulation of chromatin by histone modifications' synthesizes mechanisms. Herman et al. (1996) complements with DNA methylation detection via MSP.
Paper Timeline
Most-cited paper highlighted in red. Papers ordered chronologically.
Advanced Directions
Research centers on PRMT1 and PRMT5 in mammalian arginine methylation for cancer proliferation, with 39,285 papers but no recent preprints or news in the last 12 months indicating steady focus on established epigenetic and transcriptional pathways.
Papers at a Glance
| # | Paper | Year | Venue | Citations | Open Access |
|---|---|---|---|---|---|
| 1 | Translating the Histone Code | 2001 | Science | 9.6K | ✕ |
| 2 | THE UBIQUITIN SYSTEM | 1998 | Annual Review of Bioch... | 8.7K | ✕ |
| 3 | The language of covalent histone modifications | 2000 | Nature | 8.5K | ✕ |
| 4 | Regulation of Ferroptotic Cancer Cell Death by GPX4 | 2014 | Cell | 7.0K | ✓ |
| 5 | High-Resolution Profiling of Histone Methylations in the Human... | 2007 | Cell | 6.7K | ✓ |
| 6 | Epigenetic regulation of gene expression: how the genome integ... | 2003 | Nature Genetics | 6.2K | ✕ |
| 7 | DNA Methyltransferases Dnmt3a and Dnmt3b Are Essential for De ... | 1999 | Cell | 6.0K | ✓ |
| 8 | Mechanisms of TGF-β Signaling from Cell Membrane to the Nucleus | 2003 | Cell | 5.8K | ✓ |
| 9 | Regulation of chromatin by histone modifications | 2011 | Cell Research | 5.8K | ✓ |
| 10 | Methylation-specific PCR: a novel PCR assay for methylation st... | 1996 | Proceedings of the Nat... | 5.6K | ✓ |
Frequently Asked Questions
What is the histone code in cancer-related gene regulation?
The histone code refers to posttranslational modifications on histone amino termini that regulate chromatin structure and DNA access. Jenuwein and Allis (2001) in 'Translating the Histone Code' explain how these modifications generate synergistic or antagonistic effects on gene expression, relevant to cancer. This framework connects to arginine methylation by PRMTs in transcriptional control.
How does arginine methylation contribute to cancer?
Protein arginine methylation by PRMT1 and PRMT5 modifies histones and regulates transcription and epigenetics in mammals. These changes promote cell proliferation and are implicated in cancer. The field includes 39,285 papers on these mechanisms.
What is methylation-specific PCR used for in cancer research?
Methylation-specific PCR (MSP) detects methylation status of CpG islands after bisulfite conversion. Herman et al. (1996) in 'Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands' developed it for studying tumor suppressor silencing, imprinting, and X-inactivation. It has 5642 citations and remains key for precise mapping.
How do histone modifications regulate chromatin in cancer?
Histone modifications alter chromatin to control gene expression. Bannister and Kouzarides (2011) in 'Regulation of chromatin by histone modifications' detail mechanisms with 5796 citations. Strahl and Allis (2000) in 'The language of covalent histone modifications' describe their code-like language with 8493 citations, both central to cancer epigenetics.
What role does GPX4 play in cancer cell regulation?
GPX4 regulates ferroptotic cell death in cancer. Yang et al. (2014) in 'Regulation of Ferroptotic Cancer Cell Death by GPX4' show its inhibition induces ferroptosis, offering therapeutic potential, with 7013 citations. This links to gene regulation via oxidative stress pathways.
Why are PRMT5 and PRMT1 key in this field?
PRMT5 and PRMT1 perform arginine methylation on histones and proteins, affecting transcription and epigenetics. They drive cell proliferation in cancer contexts. Keywords from 39,285 papers highlight their central roles.
Open Research Questions
- ? How do specific arginine methylation sites on histones by PRMT1 and PRMT5 synergize with other modifications to drive oncogenic transcription?
- ? What are the precise mechanisms linking PRMT5 activity to ferroptosis resistance in cancer cells?
- ? How does the ubiquitin system interact with arginine methylation in regulating short-lived proteins during cancer cell proliferation?
- ? Which combinations of histone methylation patterns most accurately predict tumor suppressor silencing across cancer types?
- ? How do environmental signals integrate with PRMT-mediated epigenetic changes to promote cancer progression?
Recent Trends
The field maintains 39,285 works with no specified 5-year growth rate; emphasis persists on PRMT5 and PRMT1 in histone methylation and cancer without new preprints or news in the last 6-12 months, reflecting consolidation of high-citation works like Yang et al. on GPX4.
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