The Epigenome Flashcards
What is the genome?
- The complete set of genetic material in a cell
- The DNA sequence that is present in a single full set of chromosomes
What is the nucleosome?
Histone proteins and DNA forming the first level of packaging?
What is chromatin?
Is the combination of histones with DNA
What are the two types of chromatin?
Euchromatin
-Gene rich
Heterochromatin
-Gene poor
What is the packing solution?
- Nucleosomes are wound up to form 30nm fibres
- Fibres are then wound up further with scaffold proteins to generate high order structure
- Chromosomes are the most densely packed form of genomic DNA
What is the epigenome?
- Sum of all heritable changes in the genome that do not occur in the primary DNA sequence and that affect gene expression
- In other words, a change in the phenotype but not the genotype
Examples of epigenetic mechanisms
- DNA methylation
- Histone modification
- X inactivation
- Genomic imprinting
What is DNA methylation?
Is the addition of a methyl group in the 5’ position of a cytosine
What is DNA methylation catalysed by?
Catalysed by the DNA methyltransferase enzyme
What does DNA methylation require in order for the methyl group to be provided?
Requires S-adenosyl methionine to provide the methyl group
Where does DNA methylation in differentiated cells occur?
In differentiated cells, it occurs in CpG di-nucleotides
What catalyses DNA demethylation?
TET enzymes catalyse DNA demethylation
What are the effects on gene expression by DNA methylation?
-Turns transcription off by preventing the binding of transcription factors
What is histone modification?
Is the addition of chemical groups to the proteins that make up the nucleosome
How are modifications named in histone modification?
Named based on the histone, the amino acid and the actual modification
What are the 3 classes of enzymes that bind to histone tails?
- Writers
- Erasers
- Readers
What do writer enzymes do and give examples?
Writers-Enzymes that add histone modification
Examples:
-Histone acetyltransferase
-Histone methyltransferase
What do eraser enzymes do and give examples?
Erasers-Enzymes that remove histone modification
Examples:
-Histone deacetylase
-Histone demethylase
What do reader enzymes do and give examples?
Readers-Enzymes that bind to the modification and alter gene activity
Examples:
-Bromodomain and extra terminal proteins
-Chromodomain proteins
What are the roles of histone modification?
Can repress or activate transcription depending on where it occurs
What does acetylation at Lysine residue do?
Acetylation at Lysine residue relaxes the chromatin structure and makes it accessible for transcription factors
How can histone modification occur and what can their effects do?
Can occur concurrently and so their effects can interact or modify each other
What is X-inactivation?
Is the inactivation of one of the 2 X chromosome in every somatic cell in females
What does X-inactivation ensure?
Ensures that every somatic cell in all humans has the same number of active copies of every gene
What is the process of X inactivation?
- The Xist gene is transcribed as a long non-coding RNA from the x-inactivation centre and binds all over the X chromosome
- Histone acetylation is removed and DNA and histone methylation occurs
- Inactive X chromosomes is heterochromatic
How is one X chromosome still kept active during X inactivation?
Tsix is derived by transcription in the opposite direction and antagonises Xist RNA to keep one X active
What is genomic imprinting?
Is the selective expression of genes related to the parental origin of the gene copy
How are imprinted genes found?
Tend to be found in clusters
How is genomic imprinting mediated?
Is mediated by imprinting control regions
What is the process of genomic imprinting and what are essential to the process?
- One copy is silenced by DNA methylation, catalysed DMNT3a and histone methylation leading to inactivation
- LNcRNAs are essential to the process
What happens to imprinting patterns during gamete formation?
Imprinting patterns are reset during gamete formation
