Related Experiment Video
Updated: Jul 28, 2026
10:28
Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
Regulating the neoplastic phenotype using engineered transcriptional repressors.
W J Fredericks1, K Ayyanathan, F J Rauscher
1The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Cancer Letters
|February 13, 2001
Summary
Engineered repressors targeting disease genes show promise in halting cancer growth. This strategy effectively suppresses tumor formation in specific cancer cells, offering potential therapeutic applications.
Area of Science:
- Molecular biology
- Genetics
- Cancer research
Background:
- Oncogenesis involves disease gene-activated pathways.
- Targeting these pathways is crucial for cancer therapy.
- Chimeric transcriptional activators like PAX3-FKHR drive specific cancers.
Purpose of the Study:
- To apply engineered transcriptional repressors to inhibit oncogenic pathways.
- To evaluate the efficacy of synthetic repressors in suppressing malignant growth.
- To explore potential therapeutic applications of this gene repression strategy.
Main Methods:
- Engineered synthetic repressors were designed, combining PAX3 DNA binding domains with KRAB or SNAG repression domains.
- These repressors were applied to alveolar rhabdomyosarcoma tumor cells.
- The effect on malignant growth and tumorigenesis was assessed.
Main Results:
- Synthetic repressors specifically inhibited disease gene-activated pathways.
- The engineered repressors suppressed malignant growth in tumor cells.
- Tumorigenesis was suppressed in alveolar rhabdomyosarcoma cells transformed by PAX3-FKHR.
Conclusions:
- Engineered repressors offer a targeted approach to inhibit oncogenesis.
- This strategy demonstrates potential for cancer therapy by suppressing tumor growth.
- Further applications include target gene analysis, understanding repression mechanisms, and cell regulation.
Related Concept Videos
01:42What is Gene Expression?
Overview
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...
01:46Epigenetic Regulation
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
02:04Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
01:52Eukaryotic Transcription Inhibitors
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
01:37Epigenetic Regulation
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...