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Published on: June 21, 2016
Positive feedback in eukaryotic gene networks: cell differentiation by graded to binary response conversion
A Becskei1, B Séraphin, L Serrano
1European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69012 Heidelberg, Germany. becskei@embl-heidelberg.de
The EMBO Journal
|May 15, 2001
Summary
Researchers engineered a synthetic gene switch using positive feedback in yeast. This system converts continuous genetic input into a switchable cell state, mimicking analog-to-digital conversion.
Area of Science:
- Synthetic biology
- Systems biology
- Molecular and cell biology
Background:
- Gene networks utilize feedback for control.
- Positive feedback is a key regulatory mechanism in biological systems.
Purpose of the Study:
- To construct a synthetic eukaryotic gene switch using positive feedback in Saccharomyces cerevisiae.
- To investigate the conversion of continuous input into a discrete cellular output.
Main Methods:
- Construction of a synthetic gene switch utilizing positive feedback in yeast.
- Mathematical modeling to analyze the system's behavior.
- Experimental validation of the autocatalytic switch mechanism.
Main Results:
- A continuous gradient of transcriptional activator was translated into a cell phenotype switch via autocatalysis.
- Mathematical analysis revealed that positive feedback converts continuous input into a bimodal probability distribution, akin to analog-digital conversion.
- The autocatalytic switch demonstrated robustness in eukaryotic gene expression, allowing regulation of cell population states.
Conclusions:
- Positive feedback is a robust mechanism for creating switch-like behavior in eukaryotic gene expression.
- This synthetic gene switch provides insights into analog-digital conversion principles in biological systems.
- Findings have implications for understanding enhancer action and cell differentiation mechanisms.
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Transcription
Overview
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
Transcription
Transcription is the synthesis of RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in correctly synthesizing messenger RNA (mRNA). Transcriptional regulation is responsible for the differentiation of different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds of RNA Molecules
In eukaryotes,...
Transcription Can Produce Different Kinds of RNA Molecules
In eukaryotes,...
Diversity in Cell Signaling Responses
The physiological function of a cell and cellular communication are outcomes of a range of extrinsic signals, intracellular signaling pathways, and cellular responses. No two cell types express the same repertoire of signaling components. Receptors are highly selective for their cognate ligands, but once activated, they can alter multiple cellular processes such as DNA transcription, protein synthesis, and metabolic activity.
Graded and Abrupt Responses
Some signaling systems generate...
Graded and Abrupt Responses
Some signaling systems generate...
Cell Signaling Feedback Loops
Positive and negative feedback loops are crucial for regulating biological signaling systems. These feedback loops are processes that connect output signals to their inputs.
Negative feedback loops
Most signaling systems have negative feedback loops that can perform different functions such as output limiter, and adaptation.
Output limiter
Upon receiving an input signal, the cellular response rapidly increases until a threshold is reached. Beyond this threshold, a negative feedback loop...
Negative feedback loops
Most signaling systems have negative feedback loops that can perform different functions such as output limiter, and adaptation.
Output limiter
Upon receiving an input signal, the cellular response rapidly increases until a threshold is reached. Beyond this threshold, a negative feedback loop...
Forced Transdifferentiation
Transdifferentiation, also known as lineage reprogramming, was first discovered by Selman and Kafatos in 1974 in silkmoths. They observed that the moths’ cuticle-producing cells transformed into salt-producing cells. Many such cases of natural transdifferentiation occur in organisms. In humans, pancreatic alpha cells can become beta cells. In newts, the loss of the eye’s lens causes the pigmented epithelial cells to transdifferentiate into the lens cells.
Artificial transdifferentiation occurs...
Artificial transdifferentiation occurs...
Cellular Differentiation
How does a complex organism such as a human develop from a single cell? It all starts from a single fertilized egg which gives rise to a vast array of cell types, such as nerve cells, muscle cells, and epithelial cells that characterize the adult? Throughout development and adulthood, cellular differentiation leads cells to assume their final morphology and physiology. Differentiation is the process by which unspecialized cells become specialized to carry out distinct functions.
A zygote is a...
A zygote is a...

