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Control of Gene Expression

Gene Regulation is Necessary

By switching genes off when they are not needed, cells can prevent resources from being wasted. There should be natural selection favoring the ability to switch genes on and off.

A typical human cell normally expresses about 3% to 5% of its genes at any given time.

Cancer results from genes that do not turn off properly. Cancer cells have lost their ability to regulate mitosis, resulting in uncontrolled cell division.

Types of Control in Eucaryotes

Gene expression in eucaryotes is controlled by a variety of mechanisms that range from those that prevent transcription to those that prevent expression after the protein has been produced. The various mechanisms can be placed into one of these four categories: transcriptional, posttranscriptional, translational, and posttranslational.

Transcriptional - These mechanisms prevent transcription.

Posttranscriptional - These mechanisms control or regulate mRNA after it has been produced.

Translational - These mechanisms prevent translation. They often involve protein factors needed for translation.

Posttranslational - These mechanisms act after the protein has been produced.

Transcriptional

These mechanisms prevent the synthesis of mRNA.

Heterochromatin and Euchromatin

Heterochromatin is tightly wound DNA and visible during interphase. It is inactive because DNA cannot be transcribed while it is tightly wound.

Euchromatin is not tightly wound. It is active.

Example: Barr Body

One X chromosome is inactivated in females by producing a tightly-wound structure called a Barr body.

Regulatory Proteins and Transcription

Proteins called transcription factors function by binding to specific base sequences within regions of DNA called the promoter and the enhancer. The enhancer region may be located at a distance from the gene. These transcription factors are necessary for RNA polymerase to attach. Transcription begins when the factors at the promoter region bind with the factors at the enhancer region creating a loop in the DNA.

Hundreds of different transcription factors have been discovered; each recognizes and binds with a specific nucleotide sequence in the DNA. A specific combination of transcription factors is necessary to activate a gene.

The production of transcription factors is regulated by signals produced from other molecules. For example, hormones activate transcription factors and thus enable transcription. Hormones therefore activate certain genes.

Posttranscriptional Control

These mechanisms control or regulate mRNA after it has been produced.

Differential Removal of Introns

This can produce variations in the mRNA produced. Different mRNA may have different introns removed.

For example, experiments using radioactive labeling show that calcitonin produced by the hypothalamus is different from that produced by the thyroid. In each case, the same gene produces the protein.

Speed of Transport of mRNA Through the Nuclear Pores

Evidence suggests that this time may vary.

Longevity of mRNA

Messenger RNA can last a long time. For example, mammalian red blood cells eject their nucleus but continue to synthesize hemoglobin for several months. This indicates that mRNA is available to produce the protein even though the DNA is gone.

Ribonucleases

Ribonucleases are enzymes that destroy mRNA.

Messenger RNA has noncoding nucleotides at either end of the molecule. These segments contain information about the number of times mRNA is transcribed before being destroyed by ribonucleases.

Hormones stabilize certain mRNA transcripts.

Example

Prolactin is a hormone that promotes milk production because it affects the length of time the mRNA for casein (a major milk protein) is available.

Ribonulceases destroy the mRNA.

Prolactin is a hormone that promotes milk production because it affects the length of time the mRNA for casein is available.

Translational Control

These mechanisms prevent the synthesis of protein. They often involve protein factors needed for translation.

Preventing Ribosomes From Attaching

Proteins that bind to specific sequences in the mRNA and prevent ribosomes from attaching can prevent translation of certain mRNA molecules.

Initiation Factors

Initiation factors are proteins that enable ribosomes to attach to mRNA. These factors can be produced when certain proteins are needed. For example, the eggs of many organisms contain mRNA that is not needed until after fertilization. At this time, an initiation factor is activated.

Posttranslational Control

These mechanisms act after the protein has been produced.

Protein Activation

Some proteins are not active when they are first formed. They must undergo modification such as folding, enzymatic cleavage, or bond formation.

Example: Bovine proinsulin is a precursor to the hormone insulin. It must be cleaved into 2 polypeptide chains and about 30 amino acids must be removed to form insulin.

Modification of DNA

Gene Amplification

After fertilization of an ovum, large quantities of rRNA are needed to produce ribosomes. The developing embryo will need many new proteins and the large number of ribosomes can be used to produce these proteins. In frogs, genes that code for the production of rRNA are copied so that there may be more than a million copies of these genes. The genes are located in the nucleolus and enable the fertilized egg to produce rRNA rapidly.

The Immunoglobin Genes

Immunoglobins (antibodies) are proteins that are used to defend the body against foreign invaders. They are able to do this because they have a shape that matches a shape found on the invader, allowing it to become attached. Particles that have antibodies attached are quickly destroyed by other cells in the immune system. 

Our bodies contain millions of different antibodies, each produced by a type of white blood cell called a lymphocyte. A single lymphocyte can produce only one specific kind of antibody, thus, there are millions of different kinds of lymphocytes. 

The genes that code for these antibodies differ from one lymphocyte to the next because when the lymphocytes are produced, different regions of the DNA are deleted so that each lymphocyte has a somewhat different version of the genes involved.

Transposons

Transposons are segments of DNA that are capable of moving to another location, either on the same chromosome or on a different one. If a transposon inserts itself within another gene, it can prevent the gene from expressing itself. Sometimes the transposon carries a gene which can become activated if it becomes inserted downstream from an active promoter.