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In this article we will discuss about:- 1. Introduction to Gene Regulation in Eukaryotes 2. Britten and Davidson Model Related to Gene Regulation 3. Mechanism.
Introduction to Gene Regulation in Eukaryotes:
Gene regulation refers to the control of the rate or manner in which a gene is expressed. In other words, gene regulation is the process by which the cell determines [through interactions among DNA, RNA, proteins, and other substances] when and where genes will be activated and how much gene product will be produced.
Thus, the gene expression is controlled by a complex of numerous regulatory genes and regulatory proteins. The gene regulation has been studied in both prokaryotes and eukaryotes.
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The main points of gene regulation in eukaryotes are presented below:
(i) Model Developed By:
In eukaryotes, many models of gene regulation were proposed. However, the model given by R.J. Britten and E.H. Davidson in 1969 became the most popular and is widely accepted. This model is also known as gene battery model.
(ii) Organism Used:
This model is only a theoretical model and lacks sound practical proof. Even then this model is widely accepted for gene regulation in eukaryotes.
(iii) Genes Involved:
In the Britten and Davidson model of eukaryotic gene regulation, four types of genes viz:
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(i) Sensor gene,
(ii) Receptor gene,
(iii) Integrator gene, and
(iv) Producer gene are involved.
(iv) Enzymes Involved:
In the Britten and Davidson model of eukaryotic gene regulation, one enzyme viz. mRNA polymerase is involved in transcription.
Britten and Davidson Model Related to Gene Regulation:
Britten and Davidson model is also known as gene battery model.
In this model four types of genes viz:
(1) Sensor gene,
(2) Receptor gene,
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(3) Integrator gene, and
(4) Producer gene are involved in gene regulation.
A brief description of these genes in relation to gene regulation is presented below.
1. Producer Gene:
It is comparable to a structural gene in prokaryotes. It produces pre mRNA, which after processing becomes mRNA. Its expression is under the control of many receptor sites. Each producer gene may have several receptor sites, each responding to one activator.
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Thus, though a single activator can recognize several genes, different activators may activate the same gene at different times. This gene is located just near the receptor gene. This gene controls the transcription of mRNA from DNA and also synthesis of specific proteins. The producer gene starts transcription after receiving signal from receptor gene.
2. Receptor Site (Gene):
It is comparable to the operator in bacterial operon. At least one such receptor site is assumed to be present adjacent to each producer gene. It provides a link between integrator gene and producer gene. The activator RNA binds with receptor gene.
The receptor gene activates the producer gene as soon as it receives signal from the integrator gene through activator RNA. A specific receptor site is activated when a specific activator RNA or an activator protein, a product of integrator gene, binds with it.
It is also proposed that receptor sites and integrator genes may be repeated a number of times so as to control the activity of a large number of genes in the same cell. Repetition of receptor ensures that the same activator recognizes all of them and in this way several enzymes of one metabolic pathway are simultaneously synthesized.
3. Integrator Gene:
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Integrator gene is comparable to regulator gene and is responsible for the synthesis of an activator RNA molecule that may not give rise to proteins before it activates the receptor site. At least one integrator gene is present adjacent to each sensor site. It is located very near to the sensor genes. The main function of integrator gene is to start transcription after receiving signal from sensor gene.
The RNA which is transcribed by the integrator gene is known as activator RNA. This activator RNA is a link between integrator and receptor genes. Britten and Davidson proposed that the integrator gene products are activator RNAs that interact directly with the receptor genes to trigger the transcription of the continuous producer genes.
Transcription of the same gene may be needed in different developmental stages. This is achieved by the multiplicity of receptor sites and integrator genes.
4. Sensor Gene (Site):
These are signal receiving genes. These genes are very sensitive for specific signals from the cell and its environment. Sensor genes are activated by various cellular substances like enzymes, hormones and metabolites. Whenever these genes receive signals, they pass on the message to the adjacent gene (integrator) for initiation of transcription.
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A sensor site regulates activity of an integrator gene which can be transcribed only when the sensor site is activated. The sensor sites are also regulatory sequences that are recognized by external stimuli, e.g. hormones, temperature.
According to the Britten Davidson model, specific sensor genes represent sequence-specific binding sites (similar to CAP-cAMP binding site in the E. coil) that respond to a specific signal. When sensor genes receive the appropriate signals, they activate the transcription of the adjacent integrator genes. The integrator gene products will then interact in a sequence specific manner with receptor genes.
A set of structural genes controlled by one sensor site is termed as a battery. Sometimes when major changes are needed, it is necessary to activate several sets of genes. If one sensor site is associated with several integrators, it may cause transcription of all integrators simultaneously thus causing transcription of several producer genes, through receptor sites.
The repetition of integrator genes and receptor sites is consistent with the reports that state that sufficient repeated DNA occurs in the eukaryotic cells. The most attractive features of the Britten and Davidson model is that it provides a plausible reason for the observed pattern of interspersion of moderately repetitive DNA sequences and single copy DNA sequences.
Direct evidence indicates that most structural genes are indeed single copy DNA sequences. The adjacent moderately repetitive DNA sequences would contain the various kinds of regulator genes (sensor, integrator and receptor genes).
Merits and Demerits of Britten and Davidson Model:
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Merits:
1. This model is widely accepted for gene regulation in eukaryotes.
2. The mRNA is stable in eukaryotes which is unstable in prokaryotes.
Demerits:
1. This is only a theoretical model and lacks sound practical proof.
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2. The mechanism of this model is more complex than operon model of gene regulation in prokaryotes.
3. This model is lesser understood than operon model of gene regulation in prokaryotes.
Mechanism of Gene Regulation in Eukaryotes:
According Britten and Davidson model, first the sensor gene receives signal from the cell. Then integrator gene becomes active and transcribe activator mRNA molecule. This activator RNA molecule gets connected with receptor gene.
Then the receptor gene activates the producer gene, which initiates transcription of mRNA and protein synthesis. In this model, the sensor and integrator genes lie together, whereas receptor and producer genes make another group.
