Regulation of gene expression

  REGULATION OF GENE EXPRESSION

Genetic regulation is how a cell controls each gene, of all the genes in a genome.Thanks to genetic regulation, each type of cell in our body has a different set of active genes, although almost all cells in the body contain exactly the same DNA.

By having different patterns of gene expression, our cells have different sets of proteins, which makes each type of cell specialize in a unique way to do its job.

For example, one of the functions of the liver is to remove toxic substances such as alcohol from the blood. To do this, liver cells express genes that encode the subunits of an enzyme called alcohol dehydrogenase. This enzyme breaks down alcohol into a non-toxic molecule. Neurons in a person's brain do not remove toxins from the body, so they keep these genes unexpressed or "turned off." Similarly, liver cells do not send signals through neurotransmitters, so they keep genes for neurotransmitters turned off.

On the left photowe can see a liver cell. The liver cell contains proteins of the enzyme alcohol dehydrogenase. If we look at the nucleus, we see that the alcohol dehydrogenase gene is expressed to produce RNA, while the neurotransmitter gene is not expressed. RNA is processed and translated.

On the right photo we can see a neuron. Neurons contain neurotransmitter proteins. If we look at the nucleus, we see that the gene for alcohol dehydrogenase is not expressed to make its RNA, while the gene for the neurotransmitter is. RNA is processed and translated, which is why neurotransmitter proteins are found in the cell.

 

How do cells "decide" which genes to turn on?

Different types of cells express different groups of genes. However, two different cells of the same type can also have different gene expression patterns, depending on their environment and internal state.

In general, we can say that the pattern of gene expression in a cell is determined by information both inside and outside the cell.

Our cells do not make the decisions that we do, they have molecular pathways that convert information, such as the binding of a chemical signal to its receptor, into a change in gene expression.

For example how cells respond to growth factors. A growth factor is a chemical signal from a neighboring cell that tells a target cell to grow and divide. We could say that the cell "notices" the growth factor and "decides" to divide.

 

Growth factors bind to their receptors on the cell surface and activate a signaling pathway in the cell. The signaling pathway activates transcription factors in the nucleus, which bind to DNA near genes that promote division and growth, and causes its transcription into RNA. RNA is processed and exported from the nucleus, and then translated to make proteins that promote growth and division.

• The cell detects growth factor by binding the growth factor to a receptor protein on the cell surface.

• Binding of growth factor causes the receptor to change shape, which triggers a series of chemical events in the cell that activates proteins called transcription factors.

• Transcription factors bind to certain DNA sequences in the nucleus and cause the transcription of genes related to cell division.

• The products of these genes are various types of proteins that make the cell divide (promote cell growth and / or move the cell through the cell cycle).

This is just one example of how a cell can convert a source of information into a change in gene expression. There are many others, and understanding the logic of gene regulation is currently an area of ongoing research in biology.

Growth factor signaling is complex and involves the activation of many targets, including transcription factor and non-transcription factor proteins. 

Eukaryotic gene expression can be regulated in many stages.

Now we will see how the expression of genes in eukaryotes can be controlled in several stages, from the availability of DNA, to the production of mRNA, and the translation and processing of proteins.

Gene expression in eukaryotes involves many steps, and almost all of them can be regulated. Different genes are regulated at different points, and it is not uncommon for a gene to be regulated in multiple steps.

• Chromatin accessibility. The structure of chromatin (DNA and its organizing proteins) can be regulated. Chromatin that is more open or "relaxed" makes a gene more available for transcription.

• Transcription. Transcription is a key regulatory site for many genes. Transcription factor protein clusters bind to specific DNA sequences in or near a gene and promote or repress its transcription into RNA.

• Using the alternative splicing process, RNA processing can be regulated.

 

 

Stages of eukaryotic gene expression (any of which can potentially be regulated)

1. Structure of chromatin. Chromatin can be either tightly packed or loose and open.

2. Transcription. An available gene (with enough open chromatin) is transcribed to make a primary transcript.

3. Processing and export. The primary transcript is processed (spliced, the cap and a poly-A tail are added) and shipped out of the core.

4. Stability of mRNA. In the cytosol, mRNA may be stable for long periods or it may rapidly degrade (break down).

5. Translation. The mRNA can be more or less easily / frequently translated by ribosomes to make a polypeptide.

6. Protein processing. The polypeptide can undergo various types of processing, including proteolytic degradation (cutting out amino acids) and the addition of chemical modifications, such as phosphate groups

For an active protein to be present in the cell, all of these steps (if applicable) must be performed for a given gene.

• RNA stability. The lifetime of an mRNA molecule in the cytosol affects how many proteins can be made from it. Small regulatory RNAs called miRNAs can bind to target mRNAs and cause them to be cut into pieces.

•Translation. The translation of an mRNA can be increased or inhibited by regulators. For example, miRNAs sometimes block the translation of their target mRNAs (rather than causing them to be chopped up).

• The activity of the protein. Proteins can undergo a variety of modifications, such as being cut or tagged with chemical groups. These modifications can be regulated and can affect the activity or behavior of the protein.

Although all stages of gene expression can be regulated, the main checkpoint for many genes is transcription. Later phases of regulation often refine patterns of gene expression that were "approximated" during transcription.

Gene regulation and differences between species

Differences in gene regulation make the structure and function of the different cell types in a multicellular organism (such as yourself) unique. If we take a little distance, gene regulation may also help explain some of the differences in form and function between different species with relatively similar gene sequences.

For example, humans and chimpanzees have genomes that are approximately 98.8%, point, 8, percent identical at the DNA level. The protein coding sequences of some genes are different between humans and chimpanzees, contributing to the differences between species. However, the researchers also believe that changes in gene regulation play an important role in making humans and chimpanzees different from each other. For example, some regions of DNA present in the chimpanzee genome but missing from the human genome contain known gene regulatory sequences that control when, where, or how strongly a gene is expressed.