Lesson 3. Gene regulation

This lesson consists of two videos. First, you will learn about gene regulation – the epigenome and epigenetic regulation – and how environmental factors can alter an individual’s epigenome. The second video discusses the inheritance of epigenetic changes and gene imprinting and summarises what you have learned in this lesson.

Epigenome and epigenetic regulation

We learned earlier that each cell in a multicellular organism contains all the genes of the organism. So, all the information needed for the organism to grow and function from conception to death is encoded in each of its cells. The amount of genetic information is vast.

(It should be noted that cells without nuclei do not actually contain genes. Such cells include red blood cells and platelets.)

However, only a small fraction of the genes in each cell are active at any one time. Obviously, hair follicle cells in the skin do not work in the same way as the cells in the central nervous system. Each cell type uses only the information from its genes that is relevant to its own function. The genes have to work in the right way, at the right time, when the product they code for is needed. This is tightly regulated in cells.

The epigenome regulates gene expression

Genes have different regulatory factors whose job it is to switch the gene on or off. These factors are contained in the DNA code itself, or are molecules that attach to the DNA or proteins around which the DNA strand is wrapped when it is packaged. All the regulatory factors that influence gene expression together make up an individual’s epigenome.

The epigenome refers to all the factors that regulate the function of an individual’s genes. Epigenetics includes the switching on and off of genes, the imprinting of genes and the influence of environmental factors on gene function.

We also learned earlier that after fertilisation, all cells are identical to each other. They divide up without specialising in any particular function. These unspecialised cells are called stem cells. Each stem cell contains the same set of genes and the epigenome that regulates them.

The epigenome regulates cell differentiation and silences genes that are no longer needed. During ontogenesis (the development of an organism), genes that regulate the development are activated and the proteins they produce cause cells to differentiate into different tissues. For example, cells become skin cells, muscle cells and nerve cells. Once the necessary genes have been read and proteins made, the genes are switched off, often permanently, so that cell differentiation is usually irreversible.

Environmental factors can change the epigenome

The epigenome, which regulates gene function, can be altered by factors such as diet or other environmental factors. Environmental factors therefore determine which genes are read. Changes in gene expression help the cell to respond to environmental cues and adapt to new conditions. The DNA code itself does not change, but a change in the epigenome changes how it is used. For example, the quality of a pregnant female’s diet will affect the function of genes in the foetus, and when offspring are born, good care by the dam will change the epigenome of the offspring.

Epigenetic changes occur throughout life: from the conception to the last day of life. Epigenetic changes are also one of the reasons for differences in the characteristics of identical twins.

Silencing of genes

Gene silencing occurs through epigenetics. This is done by wrapping the gene so tightly that it cannot be read. And because it cannot be read, the gene cannot be made into a protein in the cell. Later on, a nutrient, for example, can cause the silencing to stop, and the gene’s function to resume. Epigenetic changes can therefore be reversed.

A tightly packed strand of DNA is called heterochromatin. Euchromatin is a loosely packed strand of DNA. In euchromatin, genes are active and being read to make proteins.

Video 2

Example of gene silencing: tortoiseshell pattern in cats

A good practical example of gene silencing is the tortoiseshell pattern of cats, which is determined by genes on the X chromosome.

In both males and females, only one X chromosome per cell is required for normal body function. In females, each cell has two X chromosomes, but only one is used and the other is silenced to equalise the dose of genes linked to the X chromosome compared to males (XY). The Y chromosome is much smaller than the X chromosome and has no matches for genes on the X chromosome.

It is completely random which X chromosome is active and which is repressed in each cell. This phenomenon is called mosaicism. Silencing is usually irreversible, so all new cells from a given cell will have the same X chromosome silenced (except in mice and marsupials, where the X chromosome to be silenced is always the one inherited from the father).

In cats this phenomenon forms a black and orange mottled pattern known as ‘tortoiseshell’. If one X chromosome in a cat has an orange gene and the other has a black colour gene (an allele – we’ll learn more about this later), some cells will be black, and some will be red. In each cell, only the X chromosome from either the sire or the dam is active.

The tortoiseshell pattern is usually only seen in females, as it requires two X chromosomes. Males are either black or red.

Did you know? Multi-coloured cats have slightly different names in different countries and continents. Tortoise is the name given to those multi-coloured cats with relatively few or no white markings. Cats that are predominantly white with additional patches of tortoiseshell colouring are called tricolour, tortoiseshell-and-white, or calico. The base colour is usually black in tortoiseshell and white in calico. Tricolour males are rare, and in Japan, for example, they are believed to bring good luck. The tricolour male cat is a genetic anomaly. For example, such a cat may have two X chromosomes or be a chimera.

Epigenetic modifications can be inherited

Studies in humans, mice and rats in recent years have revealed a revolutionary fact: some of the epigenome changes that occur during an individual’s lifetime are inherited.

What our grandparents ate can affect our health and longevity. A Swedish study* found that the grandchildren of grandparents who were deprived of food between the ages of 9 and 12 were less likely to die from cardiovascular disease. The grandchildren of men who were well nourished before puberty were four times more likely to develop adult-onset diabetes than the grandchildren of men who were poorly nourished.

Ageing can also alter the epigenome of cells, and these changes can also be inherited. Inheritance of epigenetic changes has also been found in cases where parental exposure to certain drugs or toxic substances has increased the risk of drug side effects in the offspring or increased the risk of the offspring developing certain diseases for up to several generations. Interestingly, research has shown that fear of certain things can also be inherited: babies as young as six months old can be afraid of spiders and snakes when they first encounter them.

The epigenome is particularly vulnerable to environmental influences during early gestation. Stress experienced by a mother during pregnancy can permanently alter the epigenome of her offspring, and this change can be passed on to her offspring. The quality of a pregnant mother’s diet also affects the function of her offspring’s genes.

Once the offspring are born, the mother’s care can induce permanent changes in the epigenome of her offspring. Individuals with inadequate maternal care may lack intrinsic maternal traits.

The pursuit of the best possible maternal and offspring care and well-being is also scientifically proven to be important for future generations. Neglect can have far-reaching, negative consequences. So how a pregnant female is cared for and fed, and the environment in which she is kept, really does matter.

*Kaati, Bygren, Edvinsson 2002. Cardiovascular and diabetes mortality determined by nutrition during parents’ and grandparents’ slow growth period. Eur J Hum Genet 10, 682–688. https://doi.org/10.1038/sj.ejhg.5200859

Imprinted genes

Interestingly, the expression of a gene can depend on which parent the offspring inherits it from. This phenomenon is known as genomic imprinting. In general, both paternal and maternal genes each affect the individual equally. However, an imprinted gene only works if it is passed on from the father to the offspring, or only if it comes from the mother.

Imprinted genes regulate growth, development, and various metabolic and neurological processes. For example, only the paternal version of IGF-2, a gene that affects foetal growth, works. Imprinted genes also influence social behaviour and the behaviours that are essential for early life.

There are about 100 such genes in humans and 150 in mice. Human studies have also shown that maternal forms of genes that are most active during foetal life, while paternal forms of genes become more active in adulthood.

As a result of imprinting, there is only one active gene variant in each cell. This increases the incidence of recessive diseases hidden in these genes. We will learn more about the different variants of genes and about recessive and other forms of inheritance in a moment.

What have we learned?

  • Only a small fraction of the genes in each cell are active at any one time.
  • Each gene is associated with regulatory regions in the DNA. Regulation turns the gene on, and can also turn the gene off.
  • The epigenome refers to all the factors that regulate the function of an individual’s genes.
  • The epigenome influences the reading of genes. It regulates the differentiation of cells and silences genes that are no longer needed.
  • An individual’s epigenome can be altered by diet and other environmental factors. DNA itself does not change, but a change in the epigenome can alter its function.
  • Changes in the epigenome can be passed on to offspring.
  • The expression of some genes depends on which parent the offspring inherits them from. This phenomenon is known as genomic imprinting.

Read more

Chimera. A chimera is an organism with two or more genetically distinct cell lines. Two fertilised eggs or two early embryos can fuse together to form a chimera. A fertilised egg can also fuse with an unfertilised egg or an extra sperm.

Chimeras can also be created artificially. In January 2017, the journal Science magazine reported on an experiment by researchers to develop a living human-pig chimera. The aim was to use genetic engineering to create a pig that would grow human organs for transplant.

An article in The Guardian by Desiree Schneider: The five: chimeras created by science (2019)

What do you think about the possibility of combining human and animal genes? There are certainly pros and cons. Here’s an article, also in The Guardian, by Philip Ball – discussing the ethics: Mixed messages: is research into human-monkey embryos ethical? (2021)

Information on human epigenetics in Centers for Disease Control and Prevention: What is Epigenetics?

In Wikipedia, you can read more about

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