The Epigenome Flashcards
Define the term “Genome”
- The complete set of genetic material in a cell
- OR
- The DNA sequence that is present in a single full set of chromosomes.
What are the 2 different forms of chromatin and what are some of the characteristics of both types?
- Euchromatin - Gene rich, transcriptionally active, open conformation, contains unique DNA sequences
- Heterochromatin - Gene poor, transcriptionally inactive, condensed conformation, contains lots of repetitive sequences
What is the definition of the epigenome?
The sum of all the (heritable) changes in the genome that do not occur in the primary DNA sequence but affect gene expression
Is it correct to say that all of the peigenetic chnages that occur to DNA are “heritable?”
No it is not correct to say this as the evidence for inheritance of epigenetic changes on DNA isn’t exactly clear so some epigenetic changes may not be heritable.
What mechanisms are there that can cause epigenetic changes to DNA?
- DNA Methylation
- Histone modification
- X-inactivation
- Genomic Imprinting
Explain the process of DNA methylation
- DNA methylation involves the transfer of a methyl group from S-Adenosyl methionine onto the the 5’ carbon of a Cytosine to from 5-methylcytosine
- The reaction also forms S-Adenosyl homocysteine and is catalysed by methyltransferase enzymes
What are the 3 main methyltransferase enzymes involved in the DNA methylation reaction?
- DNMT1 (DNA methyltransferase 1)
- DNMT3a
- DNMT3b
Is every cytosine within DNA able to be methylated?
- No only cytosines within CpG dinucleotides can be methylated
- This is a cytosine next to a guanine nucleotide separated by a phosphate group.
Explain the process of DNA de-methylation
- DNA de-methylation involves 5-methylcytosine being converted into a no. of different intermediates by TET (Ten-Eleven Translocation) enzymes before eventually being converted back into cytosine.
- The order of the formation of these intermediates is as follows:
- 5-methylcytosine -> 5-hydroxymethylcytosine -> 5-formylcytosine -> 5-carboxycytosine -> cytosine
Why are the different intermediates produced during DNA de-methylation?
It’s thought that these intermediates are also important in the regulation of gene expression - especially 5-hydroxymethylcytosine
What effect does DNA methylation have on gene expression?
In general, DNA Methylation prevents transcription, and therefore reduces gene expression, by preventing the binding of transcription factors to the promoter regions of particular genes.
What is histone modification?
The addition of chemical groups to the proteins that make up the nucleosome (Histone proteins).
What are some common types of histone modification?
- Histone acetylation
- Histone methylation
Where specifically on the histone protein does histone modification take place?
Histone modification takes place within the amino or carboxy terminus tail of the amino acid chain of a histone protein
What are the names for each of the histone modifications based off of?
The modifications are named based on the histone they affect; the name and position of amino acid within the amino acid sequence that they affect and the actual modification
For example, H3K4Me3 means that on Histone 3, the Lysine at position 4 is tri-methylated
Explain the process of X-inactivation?
- The Xist gene is transcribed from the X-inactivation centre (Xic) to produce a long noncoding RNA (lncRNA) which then binds all over the X-chromosome
- Binding of Xist lncRNA to the X-chromosome causes histone acetylation to be removed and results in histone and DNA methylation to occur instead.
- This causes the X-chromosome to become completely inactive
Give a real life example of X-inactivation in females
- Tortoiseshell cats - exclusively female
- They have one X chromosome with an orange fur allele and one X chromosome with a black fur allele
- Random X-inactivation in each somatic cell results in patches of orange and black fur rather than a mixture of the two.
What is genomic imprinting?
- It 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 and usually genes from both copies are expressed
- However in imprinted genes only the genes from either the maternal or paternal copy of the gene are expressed
Why are imprinting patterns reset during gamete formation?
They are reset because the imprinted genes of an adult may still be inherited by their offspring and so by resetting the imprintoing pattern it allows those genes to be expressed within the offspring.
