Regulation of Gene Expression

Gene expression can be regulated by various cellular processes with the aim to control the amount and nature of the expressed genes.

Expression of genes can be controlled with the help of regulatory proteins at numerous levels. These regulatory proteins bind to DNA and send signals that indirectly control the rate of gene expression.

The up-regulation of a gene refers to an increase in expression of a gene whilst down-regulation refers to the decrease in expression of a gene.

The control of gene expression is more complex in eukaryotes than in prokaryotes. This is because of the presence of a nuclear membrane in eukaryotes which separates the genetic material from the translation machinery.

This necessitates some additional steps such as messenger RNA (mRNA) transport and resultant eukaryotic gene regulation at many different points. In contrast, prokaryotes lack a clearly defined nucleus hence the key point at which their gene regulation occurs is during transcriptional initiation.  

Regulation of Gene Expression in Eukaryotes

In eukaryotes, the expression of biologically active proteins can be modulated at several points as follows:

Chromatin Structure

Eukaryotic DNA is compacted into chromatin structures which can be altered by histone modifications. Such modifications can result in the up- or down-regulation of a gene.

Initiation of Transcription

This is a key point of regulation of eukaryotic gene expression. Here, several factors such as promoters and enhancers alter the ability of RNA polymerase to transcribe the mRNA, thus modulating the expression of the gene.

Post-Transcriptional Processing

Modifications such as polyadenylation, splicing, and capping of the pre-mRNA transcript in eukaryotes can lead to different levels and patterns of gene expression. For example, different splicing patterns for the same gene will generate biologically different proteins following translation.

RNA Transport

After post-transcriptional processing, the mature mRNA must be transported from the nucleus to the cytosol so that it can be translated into a protein. This step is a key point of regulation of gene expression in eukaryotes.

Stability of mRNAs

Eukaryotic mRNAs differ in their stability and some unstable transcripts usually have sequences that bind to microRNAs and reduce the stability of mRNAs, resulting in down-regulation of the corresponding proteins.

Initiation of Translation

At this stage, the ability of ribosomes in recognizing the start codon can be modulated, thus affecting the expression of the gene. Several examples of translation initiation at non-AUG codons in eukaryotes are available.

Post-Translational Processing

Common modifications in polypeptide chains include glycosylation, fatty acylation, and acetylation – these can help in regulating expression of the gene and offering vast functional diversity.

Protein Transport and Stability

Following translation and processing, proteins must be carried to their site of action in order to be biologically active. Also, by controlling the stability of proteins, the gene expression can be controlled. Stability varies greatly depending on specific amino acid sequences present in the proteins.

Regulation of Gene Expression in Prokaryotes

Prokaryotic genes are clustered into operons, each of which code for a corresponding protein.

In prokaryotes, transcription initiation is the main point of control of gene expression. It is chiefly controlled by 2 DNA sequence elements of size 35 bases and 10 bases, respectively. These elements are called promoter sequences as they help RNA polymerase recognize the start sites of transcription. RNA polymerase recognizes and binds to these promoter sequences. The interaction of RNA polymerase with promoter sequences is in turn controlled by regulatory proteins called activators or repressors based on whether they positively or negatively affect the recognition of promoter sequence by RNA pol.

There are 2 major modes of transcriptional control in E. coli to modulate gene expression. Both of these control mechanisms involve repressor proteins.

Catabolite-Regulated

In this system, control is exerted upon operons that produce genes necessary for the energy utilization. The lac operon is an example of this in E. coli.

In E. coli, glucose has a positive effect on the expression of genes that encode enzymes involved in the catabolism of alternative sources of carbon and energy such as lactose. Due to the preference for glucose, in its presence enzymes involved in the catabolism of other energy sources are not expressed. In this way, glucose represses the lac operon even if an inducer (lactose) is present.

Transcriptional Attenuation

This modulates operons necessary for biomolecule synthesis. This is called attenuated operon as the operons are attenuated by specific sequences present in the transcribed RNA – gene expression is therefore dependent on the ability of RNA Polymerase to continue elongation past specific sequences. An example of an attenuated operon is the trp operon which encodes five enzymes necessary for tryptophan biosynthesis in E.coli.  These genes are expressed only when tryptophan synthesis is necessary i.e. when tryptophan is not environmentally present. This is partly controlled when a repressor binds to tryptophan and prevents transcription for unnecessary tryptophan biosynthesis.

References

• http://www.nature.com/scitable/topic/gene-expression-and-regulation-15
• http://www2.le.ac.uk/departments/genetics/vgec/schoolscolleges/topics/geneexpression-regulation
• http://www.ncbi.nlm.nih.gov/pubmed/20827583
• http://themedicalbiochemistrypage.org/gene-regulation.php
• http://www.ncbi.nlm.nih.gov/books/NBK9850/

Further Reading

• All Gene Expression Content
• A Guide to Understanding Gene Expression
• Regulatory Mechanisms Involved in Gene Expression
• Gene Expression Mechanism
• Gene Expression Measurement

Written by

Susha Cheriyedath

Susha has a Bachelor of Science (B.Sc.) degree in Chemistry and Master of Science (M.Sc) degree in Biochemistry from the University of Calicut, India. She always had a keen interest in medical and health science. As part of her masters degree, she specialized in Biochemistry, with an emphasis on Microbiology, Physiology, Biotechnology, and Nutrition. In her spare time, she loves to cook up a storm in the kitchen with her super-messy baking experiments.