Gene regulation:
The biological processes that control the frequency and manner of gene expression are referred to as gene regulation. When and where specific genes are activated, as well as the amount of protein or RNA product produced, are determined by a complex series of interactions between genes, RNA molecules, proteins (including transcription factors), and other components of the expression system. Gene expression refers to the synthesis of the polypeptide chain that are represented by a certain gene. As a result, it can be argued that gene expression can be measured in terms of the amount of protein produced by the genes. The central dogma of molecular biology is gene expression via transcription and translation, which is a fundamental concept of molecular biology.
Some genes are expressed on a regular basis because they encoded proteins that are involved in basic metabolic activities; others are expressed as part of the cell differentiation process, while others are expressed as a result of cell differentiation.
The control of gene expression:
- Each cell in the human contains all the genetic material for the growth and development of a human.
- Some of these genes will be need to be expressed all the time
- These are the genes that are involved in of vital biochemical processes such as respiration
- Other genes are not expressed all the time
- They are switched on an off at need.
Purposes of Gene Expression:
Regulated expression of genes is required for
Adaptation
Multicellular organisms’ cells react to a variety of environmental factors. Hormones and growth factors influence the structure, growth rate, and other features of these cells significantly.
Tissue specific differentiation and development
A multicellular organism’s genetic information is nearly similar in each somatic cell. Despite the fact that muscle and nerve tissue cells have drastically diverse morphologies and other characteristics, they share the same DNA. Differential gene expression is responsible for these various individual features.
Regulation of Gene Expression:
Turning genes on and off is known as gene regulation. Gene regulation can operate at any phase during the transcription-translation process, but it appears most frequently at the transcription level.
Replication level
Every inaccuracy in copying the DNA can lead to a change in expression. The shape of chromatin is crucial for controlling gene expression and replication. The packaging of DNA into nucleosomes creates a ‘closed’ structure that makes replication, transcription, and DNA repair enzymes inaccessible.
Transcriptional level
Any error in polymerization during transcription can lead to significant changes in gene expression. Eukaryotic gene expression is primarily regulated at the level of transcription beginning, while transcription can be slowed and regulated at later stages in some situations. Proteins that bind to certain regulatory regions and influence the activity of RNA polymerase control transcription in eukaryotic cells, just like in bacteria.
Post-transcriptional level
Gene expression is also regulated in the several events during post transcriptional modification (PTM) such as RNA splicing.
Translational level
The control of gene expression begins with translational regulation of mRNA. Changing the quantity or activity of rate-limiting protein components involved in translation might affect the efficiency of the translational apparatus in general, either positively or adversely.
The lac Operon
The lactose operon (also known as the lac operon) is a set of genes that are specific for uptake and metabolism of lactose and is found in E. coli and other bacteria.
Three structural genes are present in the lac operon:
- lacZ, which is the gene for -galactosidase, an intracellular enzyme that breaks down lactose into galactose and glucose.
- lacY, that encoded beta-galactoside permease, a transmembrane protein required for lactose uptake
- lacA, which is a transacetylase that transfers an acetyl group from acetyl-CoA to the hydroxyl group of galactosides.
- lacI gene, which encodes a repressor of the lac operon and is transcribed separately from the structural genes, is located at the 5′ end of the lacZ gene.
Regulation of the Lac Operon
Because prokaryotes lack a nuclear membrane, ribosomes have direct access to mRNA transcripts, allowing for quick translation into polypeptides. As a result, transcription is the rate-limiting step in bacterial gene expression and thus a significant regulatory point. The lac operon is a well-known example of bacterial gene control. Lactose digestion enzymes are produced by this operon, which is a genetic unit.
The lac operon is comprised of three consecutive structural genes that RNA polymerase transcribes as mRNA.
- At the 5′ end, an operator sequence acts as a binding site for a repressor protein that inhibits RNA polymerase.
- The lacI gene, which is not regulated, produces the repressor protein constitutively (on a continuous basis). The active tetramer is made up of subunits that self-assemble to form the repressor.
- Allolactose binds to the repressor subunits and prevents them from forming an active tetramer when present.
- Allolactose is synthesized at a constant low rate from lactose by -galactosidase, and hence serves as a lactose signal.
The catabolite activator protein is another regulatory component (CAP). In the absence of glucose, CAP combines with internal cyclic adenosine monophosphate (cAMP) to generate an active molecule that accumulates (cAMP is a starvation signal).
Only when the CAP-cAMP complex is bound does RNA polymerase successfully bind to the lac promoter. This guarantees that the lac operon is only activated when glucose is not present.
Both negative and positive control are expressed in the lac operon.
A regulatory factor is required for negative control to inhibit lac operon expression, and a regulatory factor is required for positive control to allow lac operon expression.
Negative control (conditions: presence of glucose only; prevent expression of lac operon).
The gene products from the lac operon are not required if lactose is missing and glucose is present. Lac operon expression is thus prevented by a regulatory component, the repressor protein.
It is accessible to bind to the operon and block transcription because the repressor is generated constitutively and spontaneously assembles into its active tetrameric form.
Positive control (conditions: Presence of lactose only; permit expression of lac operon)
If lactose is present but no glucose is present, the lac operon’s gene products are required to utilize the lactose for energy. As a result, a regulatory component called the CAP-cAMP complex is required for operon expression. Because cAMP is a starving signal that indicates a lack of glucose, it is accessible to form the CAP-cAMP complex and allow transcription to take place.
Positive control (conditions: Presence of both lactose and glucose; do not permit expression of the lac operon even if not prevented by repressor).
When both lactose and glucose are present, regulatory mechanisms prevent the lac operon from being overexpressed. RNA polymerase cannot connect to the promoter even when the repressor is inactivated by lactose because the CAP-cAMP complex is lacking due to the presence of glucose.
Summary:
Key points:
- Lactose metabolism genes are found in the lac operon of E. coli. When lactose is present but glucose is not, it is expressed.
- The lac repressor and catabolite activator protein are two regulators that turn the operon “on” and “off” in response to lactose and glucose levels (CAP).
- Lactose is sensed by the lac repressor. When lactose is present, it stops serving as a repressor and blocks transcription of the operon. Lactose is sensed indirectly by the lac repressor via its isomer allolactose.
- CAP, or catabolite activator protein, is a glucose sensor. When glucose levels are low, it triggers transcription of the operon. Through the “hunger signal” chemical cAMP, CAP detects glucose indirectly.
References:
- Jansen M, de Moor CH, Sussenbach JS, van den Brande JL. Translational control of gene expression. Pediatr Res. 1995 Jun;37(6):681-6. doi: 10.1203/00006450-199506000-00001. PMID: 7651749.
- Brown, T.A. and Brown, T.A., 1992. Genetics: A molecular approach (No. 04; QH506, B7 1992.). London: Chapman & Hall.
- Satyanarayana, U., 2021. Biochemistry, 6e-E-book. Elsevier Health Sciences.