the epigenome

Question 1

define genome

Answer 1

complete set of genomic material in a cell

DNA sequence present in a single full set of chromosomes

Question 2

describe the nucleosome

Answer 2

histone proteins and DNA form first level of packing

Question 3

describe packing solution

Answer 3

nucleosomes are wound to form 30nm fibres

fibres wound to further scaffold proteins to generate higher-order structures

chromosomes are most densely packed form of genomic DNA

Question 4

describe euchromatin

Answer 4

gene-rich
transcriptionally active
dispersed appearance
unique DNA sequence

Question 5

describe heterochromatin

Answer 5

gene-poor
less transcriptionally active
condensed appearance
repetitive DNA sequences

Question 6

define epigenome

Answer 6

sum of all heritable changes in genome that do not occur in primary DNA sequence and affect gene expression

epigenetic gene change results in phenotype change but not genotype

Question 7

describe the epigenome

Answer 7

central to regulation of gene expression

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

epigenetic is being used to identify novel drug targets

Question 8

list 4 epigenetic mechanisms

Answer 8

dna methylation
histone modification
x-inactivation
genomic imprinting

Question 9

describe DNA methylation

Answer 9

addition of a methyl group in the 5’ position of a cytosine

catalysed by dna methyltransferase enzymes = DNMT1, DNMT3a, DNMT3b

requires s-adenosyl methionine to provide methyl gap

differentiated cells it occurs in CpG dinucleotides

Question 10

DNA methylation and gene expression

Answer 10

dna methylation turns transcription factors off by preventing binding of tf

DNA methylation patterns change during development and are important mechanism for controlling gene expression

Question 11

histone modification

Answer 11

addition of chemical groups to proteins that make up nucleosome

large numbers of known histone modifications and many are of unknown function

large range of enzymes catalyse modification

Question 12

describe common modifications

Answer 12

methylation
acetylation
phosophorylation
ubiquination

many diff amino acids can be modified and have 1-4 groups added
gives large number of modifications

Question 13

describe histone modifiers

Answer 13

writers = acetyltransferase and methyltransferase

erasers = deacetylase
and demethylase

readers = bromodomain and extra-terminal proteins. chromodomain

Question 14

roles of histone modification

Answer 14

histone acetylation at lysine residues relax chromatin structure, reduces positive charge on histones, makes it accessible for transcription factors

histone methylation more complex and can repress or activate transcription depending on where it occurs

histone modifications occur concurrently and so their effects will interact

Question 15

x-inactivation described 1

Answer 15

inactivation of one of two X chromosomes in every somatic cell in females

needed as Y chromosome has virtually no genes, there is only one copy of each X chromosome gene in males

x inactivation ensures every somatic cell in humans has the same number of active copies of every gene

Question 16

x activation described 2

Answer 16

Xist gene is transcribed as long noncoding RNA from X inactivation centre and binds all over x chromosome

histone acetylation removed and histone and DNA methylation occurs

inactive X chromosome heterochromatic

Tsix is derived by transcription in opposite direction and antagonises Xist RNA to keep one X active.

Question 17

what is imprinting

Answer 17

imprinting is selective expression of genes related to parental origin of gene copy

every autosomal gene has one paternal and one maternal copy

imprinted genes tend to be found in clusters

very few imprinted genes

Question 18

imprinted genes

Answer 18

imprinting mediated by imprinting control regions

one copy is silenced by DNA and methylation catalysed by DNMT3a and histone methylation leading to inactivation

LncRNAs are essential to the process

imprinting patterns are reset during gamete formation

Question 19

cancer epigenetics

Answer 19

global DNA methylation is altered in tumour cells

epigenetic enzymes are often mutated in tumour cells

Question 20

pharmacoepigenetic drugs

Answer 20

DNA methyl transferase inhibitors

histone deacetylase inhibitors

seven drugs FDA-approved so far