The epigenome Flashcards
Define genome
- The complete set of genetic material in a cell
* The DNA sequence that is present in a single full set of chromosomes
Describe the packing solution
- Nucleosomes are wound up to form 30nm fibres
- Fibres are then wound up further with scaffold proteins to generate higher-order structures
- Chromosomes are the most densely packed form of genomic DNA
Define euchromatin and hetrochomatin
Gene poor and gene-rich
refer to the diagram
What is the epigenome and what does it result in?
- The sum of all the (heritable) changes in the genome that do not occur in the primary DNA sequence and that affect gene expression
- An epigenetic change results in “A change in phenotype but not in genotype”
What is the function of the epigenome?
• The epigenome is central to the regulation of gene expression
How can gene expression be regulated?
- DNA methylation and histone modification are mechanisms by which gene expression is regulated
- X-inactivation and imprinting are important epigenetic mechanisms for controlling expression from groups of genes
What are the 4 epigenetic mechanisms?
- DNA Methylation
- Histone modification
- X-inactivation
- Genomic Imprinting
What is DNA methylation?
What is it catalysed by?
What does it require?
• DNA methylation in humans is the addition of a methyl group in the 5’ position of a Cytosine
• This is catalysed by DNA methyltransferase enzymes
o DNMT1, DNMT3a and DNMT3b
• It requires S-Adenosyl Methionine to provide the methyl group
How does DNA methylation regulate gene expression?
- In general, DNA Methylation turns transcription off by preventing the binding of transcription factors
- DNA methylation patterns change during development and are an important mechanism for controlling gene expression
Give some common examples of histone modifications
What is histone modification?
Histone modification
• This is the addition of chemical groups to the proteins that make up the nucleosome
• There are a large number of known histone modifications (>100) and many are of unknown function
• Large range of enzymes catalyse modification
Common Modifications
• Methylation
• Acetylation
• Phosphorylation
• Ubiquitination
• Many different amino acids can be modified and they may have 1-4 groups added
• This gives the large number of modifications
• Others are known but poorly understood
- Modifications are named based on the histone, the amino acid and the actual modification
- For example, H3K4Me3 means that on Histone 3, the Lysine (K) at position 4 is tri-methylated
Name the histone writers, readers and erasers
Writers • Histone Acetyltransferase - HAT1 • Histone Methyltransferase - EHMT1 Erasers • Histone Deacetylase - HDAC1 • Histone Demethylase - KDM1 Readers • Bromodomain and extra-terminal (BET) proteins – BRD2 • Chromodomain proteins – CBX1
What does histone acetylation and methylation do?
- Histone acetylation at Lysine residues relaxes the chromatin structure, by reducing positive charge on the histones, and makes it accessible for transcription factors
- Histone methylation is more complex and can repress or activate transcription depending on where it occurs
- Histone modifications can occur concurrently and so their effects will interact
What is X inactivation and why do males not need it?
- This is the inactivation of one of the two X chromosomes in every somatic cell in females
- This is needed as the Y chromosome has virtually no genes, so there is only one copy of each X chromosome gene in males (hemizygosity)
- X-inactivation ensures that every somatic cell in all humans has the same number of active copies of every gene
Describe the mechanism of X inactivation
- The Xist gene is transcribed as a long noncoding RNA (lncRNA) from the X-inactivation centre (Xic) and binds all over the X-chromosome
- Histone acetylation removed and histone and DNA methylation occurs
- Inactive X-chromosome is heterochromatic – Barr body
- Tsix is derived by transcription in the opposite direction and antagonises Xist RNA to keep one X active
- All tortoiseshell cats are female
- Tortoiseshell cats have one X with an orange fur allele and one X with a black fur allele
- Random X-inactivation results in patches of orange and black fur
What is imprinting?
- Imprinting is the selective expression of genes related to the parental origin of the gene copy
- Every autosomal gene has one paternal and one maternal copy
- Imprinted genes tend to be found in clusters
- There are very few imprinted genes (~250)
