The Epigenome Flashcards
What is the nucleosome made up of?
Histone proteins and DNA
What are the features of euchromatin?
Gene rich, Transcriptionally active, less wound up and unique DNA sequences
What is another name for euchromatin?
Compartment A
What are the features of heterochromatin?
Gene poor, less Transcriptionally active, condensed appearance and a repetitive DNA sequence
What is another name for heterochromatin?
Compartment B
What is a definition for the epigenome?
The sum of all (heritable) changes in the genome that doesn’t occur in the primary DNA sequences and that affect gene expression
What does a change in the epigenome result in?
A change in the phenotype, not the genotype
What are the mechanisms that regulate gene expression?
DNA methylation and histone modification
What is DNA methylation?
Addition of a methyl group in the 5’ position of a cytosine
What is DNA methylation?
Addition of a methyl group in the 5’ position of a cytosine
What is DNA methylation catalysed by?
DNA methyltransferase enzymes
Which DNA methyltransferase enzymes catalyse DNA methylation?
DNMT1, DNMT3a and DNMT3b
What provides the methyl group for DNA methylation?
S-adenosyl methionine
Where does DNA methylation occur in differentiated cells?
CpG dinucleotides
What does DNA demethylation do?
Turns transcription off by preventing the binding of transcription factors
What is histone modification?
Addition of chemical groups to the histone
What are the four common modifications?
Methylation, acetylation, phosphorylation and ubiquitination
How are the modifications named?
Based on the histone, amino acid and actual modification
What are the three types of histone modifiers?
Writers, readers and erasers
What are the two examples of writers?
Histone acetyltransferases and histone methyltransferases
What are the writers?
Enzymes that add histone modifications
What are the readers?
Proteins that bind to histone modifications and alter gene activity and protein production
What are two examples of readers?
Bromodomain and extra-terminal proteins and chromodomain proteins
What are erasers?
Enzymes that remove histone modifications
Give some examples of erasers?
Histone deacetylase and histone demethylase
What does histone acetylation at lysine residues do?
Relax the chromatin structure by reducing the positive charge on the histones, making it accessible for transcription factors
What can histone methylation do?
Can repress or activate transcription depending on where it occurs
What is X-inactivation?
Inactivation of one of the two chromosomes in every female somatic cell
Why is X-inactivation necessary?
Needed as the Y chromosome has almost no genes
What is the process of X-inactivation?
The X-ist gene is transcribed as long non coding RNA from the X-inactivation centre and binds all over the X-chromosome
Histone acetylation is removed and histone and DNA methylation occurs
Inactive X-chromosome is heterochromatic
Tsix is derived by transcription in the opposite direction and antagonises Xist RNA to keep one X active
Why are all tortoiseshell cats female?
Random X inactivation results in random patches of orange and black fur
What is gene imprinting?
The selective expression of genes related to the parental origin of the gene copy
What are imprinted genes mediated by?
Imprinting control regions
What are essential to the genetic imprinting process?
Long noncoding RNAs
When are imprinting patterns reset?
During gamete formation
How is the non-imprinted gene inactivated?
DNA methylation and histone methylation
What is pharmacoepigenetics split into?
Epigenetic regulation of genes and epigenetic effects of drugs
What does the changing the Epigenetic regulation of genes do?
Increasing the efficacy of drugs
What does changing the epigenetic effects of drugs do?
New paradigms for drug treatment
What are the epigenetic enzymes that are normally mutated in tumour cells?
DNMT3A and TET1/2 Histone acetyltransferases Histone methyltransferases Histone kinases Histone readers Histone demethylases
Give some examples of pharmacoepigenetic drugs
DNA methyltransferase inhibitors and histone deacetylase inhibitors