Controlling Gene Expression

Development of Organisms

What is gene expression?

The process by which information in a gene is used to produce a functional product, usually a protein.

Why do different types of cells have different structures and functions even though they contain the same genes?

Different genes are switched on and expressed in different cell types, so they produce different proteins.

Approximately how many genes are present in human cells?

About 20,000–25,000 genes.

Approximately how many genes may be actively expressed in a differentiated cell?

About 10,000–20,000 genes.

What are the two main stages involved in gene expression?

Transcription of DNA into mRNA and translation of mRNA into protein.

At which stages can gene expression be controlled?

At transcription, RNA processing, translation and after translation through modification of proteins.

Why does controlling transcription provide effective control of gene expression?

A single mRNA molecule can be translated many times, producing many protein molecules, so controlling mRNA production strongly affects protein production.

What are transcription factors?

Proteins that bind to DNA in the nucleus and affect the transcription of genes.

What is a promoter sequence?

A specific region of DNA to which transcription factors and RNA polymerase bind to initiate transcription.

Where are promoter sequences usually found?

Just before the start of the gene being transcribed.

How can transcription factors stimulate gene expression?

They bind to regulatory DNA sequences and help initiate or increase transcription.

What is an enhancer sequence?

A specific region of DNA to which transcription factors bind to regulate gene activity by altering chromatin structure.

How can transcription factors affect chromatin?

They can make chromatin more or less open to RNA polymerase, increasing or decreasing transcription.

What type of chromatin structure is associated with active gene expression?

Open, loosely packed chromatin.

What type of chromatin structure is associated with inactive genes?

Closed, tightly packed chromatin.

Can regulatory sequences be located far away from the gene they control?

Yes. Regulatory sequences may be thousands of base pairs away from the gene.

Can more than one transcription factor control a single gene?

Yes. Several different transcription factors may be involved in controlling the expression of one gene.

Can one transcription factor affect several genes?

Yes. A single transcription factor may regulate several different genes.

How can one transcription factor have different effects on different genes?

It may stimulate the expression of one gene while suppressing another.

How does differential gene expression contribute to cell differentiation?

Different transcription factors switch different genes on and off, causing cells to produce different proteins and become specialised.

What is RNA splicing?

The process in which introns are removed from pre-mRNA and exons are joined together to produce mature functional mRNA.

What are exons?

Sections of DNA or RNA containing information that can code for a protein or polypeptide sequence.

What are introns?

Non-coding sections of DNA or RNA that do not code for a protein or polypeptide sequence.

Are exons or introns expressed?

Exons are expressed, whereas introns are removed from pre-mRNA.

What is pre-mRNA?

The initial RNA molecule transcribed directly from DNA before it has been modified.

Why must pre-mRNA be modified?

It contains introns that must be removed before functional mature mRNA is produced.

What are spliceosomes?

Enzyme complexes that act on pre-mRNA, removing introns and joining exons together.

What happens to introns during RNA splicing?

They are removed from the pre-mRNA.

What happens to exons during RNA splicing?

They are joined together to form mature mRNA.

What is alternative RNA splicing?

The joining of exons in different combinations to produce different mature mRNA molecules from the same gene.

How can a single gene produce several different proteins?

Alternative RNA splicing produces different mature mRNA molecules containing different combinations of exons, which are translated into different polypeptides.

Why can the number of proteins produced by an organism be greater than the number of genes?

A single gene can produce several different proteins through processes such as alternative RNA splicing.

What is post-translational modification?

The modification of a protein after it has been synthesised.

Give examples of post-translational modification

A protein may be shortened, lengthened or combined with other molecules or proteins.

How can post-translational modification increase protein diversity?

The same polypeptide can be modified in different ways to produce different functional proteins.

What is epigenetics?

The study of changes in gene expression caused by factors other than changes to the DNA base sequence.

Does epigenetic modification change the DNA base sequence?

No. It alters gene activity without changing the underlying DNA base sequence.

What factors can cause epigenetic changes?

Internal stimuli and environmental factors such as hormones, diet, body mass and other environmental conditions.

Can epigenetic changes persist through cell division?

Yes. Some epigenetic modifications can be passed on when cells divide by mitosis.

What are three major mechanisms of epigenetic control?

DNA methylation, histone modification and non-coding RNA.

What is DNA methylation?

The addition of a methyl group (–CH₃) to DNA.

Where does DNA methylation commonly occur?

At cytosine bases next to guanine bases in CpG sites.

Which enzyme adds methyl groups to DNA?

DNA methyltransferase.

What effect does DNA methylation usually have on gene expression?

It silences genes by preventing transcription.

How does DNA methylation prevent transcription?

It changes the arrangement of DNA and makes it less accessible to the transcription machinery.

What is gene silencing?

The prevention or reduction of expression of a gene.

Give important roles of DNA methylation

DNA methylation is involved in embryonic development, cell differentiation and X chromosome inactivation.

What is DNA demethylation?

The removal of methyl groups from methylated DNA.

What effect does DNA demethylation have on gene expression?

It can activate genes by making them available for transcription.

Why is DNA demethylation important?

It allows previously silenced genes to become active and be transcribed.

How is abnormal DNA methylation associated with cancer?

Abnormal methylation or demethylation can alter the activity of genes involved in controlling cell growth and division.

What are histones?

Positively charged proteins around which DNA winds to form chromatin.

What is chromatin?

The DNA–protein complex that makes up chromosomes.

How does chromatin structure affect gene expression?

Loosely packed chromatin makes DNA accessible for transcription, whereas tightly packed chromatin prevents genes from being transcribed.

What is heterochromatin?

Densely supercoiled and condensed chromatin in which genes are generally unavailable for transcription.

Why are genes in heterochromatin usually inactive?

The tightly packed DNA is inaccessible to the proteins required for transcription.

What is active chromatin?

Loosely packed chromatin in which DNA is accessible to transcription factors and RNA polymerase.

What is histone modification?

Chemical modification of histone proteins that changes chromatin structure and therefore affects gene expression.

What is histone acetylation?

The addition of an acetyl group to lysine residues in histone proteins.

What effect does histone acetylation usually have on chromatin?

It opens up the chromatin structure.

How does histone acetylation affect gene expression?

It makes DNA more accessible for transcription and therefore usually activates gene expression.

What happens when acetyl groups are removed from histones?

Chromatin becomes more condensed, forming heterochromatin and reducing transcription.

What is histone methylation?

The addition of a methyl group to lysine residues in histone proteins.

What effect can histone methylation have on gene expression?

Depending on where methylation occurs, it can either activate or inactivate a region of DNA.

How can hormones affect gene expression?

Hormones can trigger changes in chromatin structure that switch particular genes on or off.

How does ecdysone affect gene expression in insects?

Ecdysone causes regions of chromosomes to open up, allowing genes to be transcribed and proteins required for moulting to be produced.

What are chromosome puffs?

Regions of insect chromosomes where chromatin has opened up and genes are being actively transcribed.

Why do chromosome puffs form?

Chromatin becomes less condensed, making DNA accessible for transcription and causing large amounts of mRNA to be produced.

What is non-coding RNA (ncRNA)?

RNA that does not code for proteins but can regulate transcription, modify transcription products or alter chromatin structure.

Approximately what proportion of transcribed human RNA does not code for proteins?

About 98%.

How can non-coding RNA regulate gene expression?

It can silence genes, modify products of transcription or alter chromatin structure.

What is X chromosome inactivation?

The silencing of one X chromosome in cells of female mammals.

Why does X chromosome inactivation occur?

It helps balance the amount of X-linked gene products produced in XX females and XY males.

What is Xist?

A non-coding RNA involved in X chromosome inactivation.

How does Xist cause X chromosome inactivation?

Xist RNA coats one X chromosome and causes it to become condensed and transcriptionally inactive.

What is a Barr body?

A condensed, inactive X chromosome found in female mammalian cells.

What happens to the inactive X chromosome after Xist acts on it?

It coils and condenses to form a stable Barr body.

How can non-coding RNA affect chromatin modification?

It can act on histones and change whether regions of DNA are available for transcription.

What is cell differentiation?

The process by which an unspecialised cell becomes specialised for a particular function.

How does gene expression cause cell differentiation?

Different genes are switched on and off, causing cells to produce specific proteins that determine their specialised structure and function.

What role does epigenetics have in cell differentiation?

Epigenetic modifications switch particular genes on or off so that specialised cells produce the proteins required for their functions.

Which epigenetic mechanisms are important in cell differentiation?

DNA methylation, DNA demethylation and histone modification.

What can trigger epigenetic changes during cell differentiation?

Chemical stimuli, transcription factors and environmental signals.

What happens after certain genes are activated during differentiation?

mRNA is produced from the genes and translated to form specific polypeptides or proteins.

How can epigenetic changes produce permanent changes to a cell?

Once genes have been switched on or off, the epigenetic modifications can be maintained through mitosis, preserving the specialised cell type.

Summarise the process of cell differentiation through gene regulation

A stimulus or transcription factor causes epigenetic changes → specific genes are activated → mRNA is produced → mRNA is translated into proteins → the proteins permanently modify the cell’s structure and function.

What is the relationship between DNA methylation and transcription?

DNA methylation usually prevents transcription.

What is the relationship between histone acetylation and transcription?

Histone acetylation usually opens chromatin and enables transcription.

How can phenotype be influenced without changing genotype?

Environmental and internal factors can cause epigenetic modifications that alter which genes are expressed without changing the DNA base sequence.

Why can cells with the same DNA have very different phenotypes?

Different cells have different patterns of gene expression caused by transcription factors and epigenetic modifications, so they produce different proteins.