The Epigenome Flashcards
What is the genome?
The complete set of genetic material in a cell
How is the genome organised?
It exists in a cell as an organised structure made up of a number of macromolecules with DNA as the primary building block. Histones and other proteins provide a support around which the DNA is wound. These structures are then organised in 3D to form fibres and ultimately chromosomes
What is a nucleosome?
Histone proteins and DNA that forms the first level of packaging
How is DNA packaged?
- Nucleosomes are wound to form 30nm fibres
- Fibres are wound up further with scaffold proteins to generate higher-order structures
- Chromosomes are the most densely packed form of genomic DNA
What is the epigenome?
The sum of all the heritable changes in the genome that do not occur in the primary DNA sequence and that effect gene expression.
What is an epigenetic change?
A change in phenotype but not in genotype
What are the epigenetic mechanisms?
DNA methylation
Histone modification
X-inactivation
Genomic imprinting
What is DNA methylation?
It is the addition of a methyl group in the 5’ position of a cytosine.
What catalyses DNA methylation?
DNA methyltransferase enzymes
What are the DNA methyltransferase enzymes?
DNMT1, DNMT3a and DNMT3b
What provides the methyl group in DNA methylation?
S-Adenosyl Methionine
How does DNA methylation occur in differentiated cells?
It occurs in CpG dinucleotides
How is DNA demethylated?
Through a series of steps:
1. 5-methylcytosine is converted via TET into 5-hydroxymethylcytosine as there is an addition of an OH onto the 5th carbon.
- Then TET converts this into 5-formylcytosine (an aldehyde).
- Then TET converts this into 5- carboxycytosine as an COOH group is added.
- TDG and BER occur to convert 5-carboxycytosine, 5-formylcytosine or 5-hydroxycytosine back into cytosine through passive demethylation.
What is TET?
It is Ten-Eleven Translocation enzyme
What is TDG?
Thymidine DNA glycosylase
What is BER?
Base Excision Repair
When does passive demethylation occur?
It occurs during replication
What is the importance of DNA Methylation?
- Turns off transcription by preventing binding of the transcription factors.
- Patterns change during development and are an important mechanism for controlling gene expression
What is histone modification?
- The addition of chemical groups to the proteins that make up the nucleosome.
How many histone modifications are there and what is there function?
About 100 modifications and many are of unknown functino
What are the common histone modifications?
Acetylation and Methylation
How are histone modifications named?
Based on the histone, the amino acid and the actual modification. For example, H3K4Me3 means on histone 3, the lysine at position 4 and it is tri-methylated
What are histone writers? Give examples
Enzymes that add histone modifications. For example - Histone Acetyltransferase - HAT1
- Histone Methyltransferase - EHMT1
What are histone erasers? Give examples
Enzymes that remove histone modifications.
For example:
- Histone deactylase HDAC1
- Histone demethylase KDM1