Epigenetics

Genome

Hereditary information encoded in DNA.

Epigenome

The sum of all the factors that determine when, where, which genes are “switched on” or expressed.

Epigenetics overview

The study of the changes in organisms caused by the modification of gene expression, rather than the alteration of the genetic code. (ie a phenotypic change, without a genotypic change). For example, it can interfere with the transcription and translation process involved in protein production.

Gene expression

• The process by which information from a gene is used in the synthesis of proteins or RNA. It is these proteins that determine a phenotype. (E.g. physical traits, disease).

• Genes can be turned “on” or “off” to create proteins to control the function of the cell. (E.g. When a cell needs to create a signal to another cell, part of the cell cycle, age of the cell).

Epigenetics

• The changes in gene expression that result from mechanisms other than changes in the genes.

• There is a growing list of environment factors that cause epigenetic changes that cause epigenetic changes that can be inherited by offspring.

Changing the structure of chromatin

Gene expression can change the way in which the DNA is wrapped around the histone changes.

Ways the structure of chromatin can change

• Histone modification

• Acetylation

• Methylation

Histone modification

• Changes the amino acids in a histone.

• Changes the shape of the histone.

• This shape is copied each time that DNA is replicated.

• This ensures that a particular specialised cell always remains the same and doesn’t revert back to a stem cell.

• This happens regularly throughout normal gene expression.

Acetylation

The addition of an acetyl group to the histone.

• Reduces = the attraction between the histone and DNA.

• DNA = wound more loosely around the histone.

• Allows = RNA polymerase greater access to the gene resulting in increased transcription.

• Enhances = gene expression.

Methylation

Adds a methyl group to the DNA.

• Occurs = at CpG sites (where Cytosine is next to Guanine)

• Blocks access to = the gene for RNA polymerase

• Results in = decrease in transcription

• Inhibits = gene expression

• Can also methylate the histone

• Demethylation may also occur which is the opposite (enhances gene expression).

Environmental factors that can influence epigenetic change

• Severe stress

• Nutritional factors

• Toxins or drugs that enter cells

Epigenetic inheritance

Some epigenetic tags remain in place as genetic information passes from one generation to another.

This means that a parent’s experiences, in the form of epigenetic tags, can be passed down to future generations.

Epigenetic tags

Act as a kind of cellular memory. A cell’s epigenetic profile (a connection of tags that tell genes whether to be on or off) is the sum of the signals it has received during its lifetime.

Experiences are passed to daughter cells

• As cells grow and divide, cellular machinery faithfully copies epigenetic tags along with the DNA.

• This is especially important during embryonic development, as past experiences inform future choices. A cell must first “know” that it is an eye cell before it can decide whether to become part of the lens or the cornea.

• The epigenome allows cells to remember their past experiences long after the signals fade away.

Nurturing behaviour in rats

Rat pups who receive high or low nurturing from their mothers develop epigenetic differences that affect their response to stress later in life.

When the female pups become mothers themselves:

• High nurtured pups - become high nurturing mothers (and vice versa)

• The nurturing behaviour itself transmits epigenetic information onto the pups’ DNA, without passing through egg or sperm.

The Dutch Famine Birth Cohort

Prenatal exposure to the famine had permanent effects on the health outcomes that emerged later in life among the offspring. People who were in utero during the famine suffered a variety of physical and mental issues as adults. The two main lessons reported out in this journal article were:

1. There were effects of prenatal famine exposure in the absence of effects on body size at birth. In other words, in spite of adaptations that enable the foetus to grow to a normal size during famine, undernutrition still had adverse, long-term health consequences.

2. The effects of undernutrition in the womb depended on the timing of when organs and systems were developing.