Epigenetics Flashcards
1
Q
Epigenetics
A
Epigenetics refers to changes in gene expression as a result of changes in chemicals (non-DNA material) rather than changes to the genes in DNA (DNA material)
2
Q
Genome
A
- The human genome is the complete assembly of DNA (about 3 billion base pairs) that makes each individual unique
- This includes any mutations that may have occured to genes during DNA replication which are passed onto daughter cells
- DNA holds the instructions for building proteins that carry out a variety of functions in a cell*
- A protein will be made when a gene expressed is ‘turned on’*
3
Q
What regulates gene expression?
A
- A human being has trillions of cells, specialized for different functions in muscles, bones and the brain, and each of these cells carries essentially the same genome in its nucleus
- the difference among cells are determined by how and when different sets of genes are turned on or off (silenced) in various kinds of cells
- the specialised cells in the eye turn on genes that make proteins that can detect light
- specialised cells in red blood cells make proteins that carry oxygen from the air to the rest of the body
- Various factors influence gene expression including: age of cell, time of day, hormones and the environment
- The EPIGENOME can also play a role in controlling mant of these changes in gene expression
4
Q
Epigenome
A
- The epigenome is made up of chemical compounds and proteins that attach to DNA and turn genes on or off, controlling the production of proteins in particular cells
- Epigenic regulation of gene expression is achieved by modifying the chromatin (the tightly packed complex of proteins and DNA)
- When such epigenomic compounds attach do DNA the genome is said to have “epigenetic marks”
- These marks are sometimes passed on from cell to cell as cells divide. They also can be passed down from one generation to the next.
- To affect gene expression the epigenome modified the chromatin and marks the DNA genome in 2 main ways:
1. Histone modification
2. DNA Methylation
5
Q
Histone Modification
A
- DNA is tightly coiled around special proteins called HISTONES and is referred to as chromatin
- If the way in which DNA is wrapped around the histone protein changes then gene expresison will be altered
6
Q
Histone Modification - the way DNA wraps around histones can be changed
A
The way DNA wraps around histones can be changed in one of two ways:
-
Changes to the amino acids that make up the histone proteins
* These changes can alter the shape of the histone and allow for gene expression. This can allow for cell differentiation to occur. - The addition of an acetyl group (CH3CO) to the histone protein
- Acetylation activates gene expression by making the DNA less tightly bound to the histone proteins, allowing RNA polymerase easier access to the DNA. This means that gene transcription is more likely to occur
- Deacetylation represses gene expression (gene silencing) making it harder for gene transcription to occur
- Changes in the histone can be passed onto the daughter cells
7
Q
Histone Modication Summary
A
Deacetylation
- the removal of an acetyl group from a histone
- condenses chromatic structure
- harder for transcription of gene to occur
Acetylation
- addition of an acetyl group to the histone
- opens condensed chromatic structure
- transcription of gene more likely to occur
8
Q
DNA Methylation - what happens
A
- This is the addition of a methyl group (CH3) to the DNA itselft to inhibit gene expression forever in an individual
- The methyl group binds to the cytosine bases on DNA if they occur next to guanine bases (an area known as CpG sites - Cytosine - phosphorus - Guanine sites)
- The binding forms 5-methylcytosine
- It has the effect of densely packing the DNA making it less accessible to RNA polymerase
- as a result less transcription occurs in areas with high methylation (high levels of 5-methlycytosine)
- In other words, methylation inhibits gene expresison/turns genes off (silences them)
9
Q
DNA Methylation - Impacts and Influences
A
- methylation patterns are passed onto daughter cells and can affect germ lines cells. As a result a person’s offspring can inherit the new methylation patterns
- methylation can be influenced by environmental factors and DNA is thought to show changes in methylation patterns as a person ages
- this is thought to again explain why identical twins show greater differences in their phenotype as they age. Although their DNA base sequence is identical, they develop different patterns of methylation due to differing influences in their environment. As a result different genes can be surpressed
- DNA methylation inhibits gene expression forever
10
Q
Genomic Imprinting
A
- For most genes, we inherit two working copies: a maternal and paternal set
- But with imprinted genes, we inherit only one working copy of the gene. Only one set of gene is being expressed:
- Either the maternal or paternal copy of the gene has been epigenetically silenced
- This silencing occurs through the addition of methyl groups during egg or sperm formation
What difference does impriting make?
- Non imprinted genes = usually after egg and sperm meet, the zygote is epigenetically reprogrammed. Meaning most of its epigenetic tags are stripped from the DNA.
- Imprinted genes = after egg and sperm meet, the imprinted genes in the zygote keep their epigenetic tags. Imprinted genes begin the process of development with these epigenetic tags in place and pass them onto daughter cells.
11
Q
Impriting is required for normal development
A
- Imprinting is a normal proces, which occurs in about 1% of genes. So an individual has one active copy of an imprinted gene.
- However, improper imprinting can result in an individual having two active copies or two inactive copies of a gene. This can be lead to severe development abnormalities, cancer and other problems.
12
Q
Prader-Willi and Angelman Syndrome
A
- They are two very different disorders, but are both linked to the same imprinted region of chromosome 15
- Both conditions are caused by deletions or mutations to chromosome 15
- If there is deletion in this imprinted region on the paternal chromosome 15, neither (paternal nor maternal) chromosome 15 will express the genes in the PWS region. As a result, the child will have PWS
- However, if the deletion is on the maternal chromosome 15, then neither (paternal nor maternal) chromosome 15 of the child will express the genes in the AS region, and hence, this child will have AS.
13
Q
Prader-Willi Syndrome
A
- If paternal chromosome is affected
- symptoms include learning difficulties, short stature and compulsive eating
- individuals are missing gene activity that normally comes from dad
- happens when dad’s copy is missing or when there are two maternal copies
14
Q
Angelman Syndrome
A
- If maternal chromosome is affected
- symptoms includes learning difficulties, speech problems, seizures, jerky movements and an unsually happy disposition
- individuals are missing gene activity that normally comes from mum
- happens when mum’s copy is defective or missing or when there are two paternal copies
15
Q
Transgenerational Epigenetic Effects
A
- its been observed that changes in the epigenome due to environmental effects have been passed through germline cells to subsequent generations
- environmental factors that are thought to affect the epigenome include: diet, stress, smoking and pesticides
