Week 5

Question 1

What is phenotype determined by

Answer 1

Genotype and environment (epigenetics mechanism)

Question 2

What are alleles

Answer 2

Different versions of same gene

Question 3

What is epigenetics

Answer 3

The study of changes in organism caused by modification of gene expression rather than alteration of genetic code itself

Question 4

Differentiation

Answer 4

Patterns of gene expression change
A less specialised cell undergoes maturation to become more distinct in form and function
Immature cells become mature cells with specific functions

Question 5

Different cell types express the same proteins

Answer 5

Some proteins you found in all cells types as they’re important for cellular functions
‘Housekeeping genes’- gene expressed in all cells
E.g. neuron and skeletal muscle- Same genome, common structural proteins and enzymes e.g. histones, RNA polymerase, tubulin, pyruvate kinase etc

Question 6

Different cell types express different proteins

Answer 6

E.g. neuron and skeletal muscle
Same genome
Specialised proteins e.g. neuron- acetyl choline esterase and skeletal muscle- troponin
Genes turned on, or turned off but in cell-type specific pattern

Question 7

What regulates gene expression

Answer 7

1. Transcriptional control (predominant level of control)
2. RNA processing control
3. RNA transport and localisation control
4. Translation control
5. MRNA degradation control
6. Protein activity control

Question 8

What is a gene

Answer 8

Genes are transcriptional units composed of:
- structural information coding for a protein
-regulatory sequences giving instructions for expression

Question 9

Regulatory sequences

Answer 9

Control gene expression
Upstream of transcriptional start site- promoter
Happen at a distance from gene- enhancer
5’ regulatory sequence controls transcription initiation= gene promoter

Question 10

Gene regulation- general transcription factors

Answer 10

RNA polymerase cannot recognise transcription start sites
General transcription factors:
Recognise & bind the gene promoter
Recruit RNA polymerase II
Allow a ‘basal’ (low) level of transcription

Question 11

Activated gene regulation

Answer 11

Rates of transcription are controlled by:
Enhancers (5’ or 3’, or within introns, far away)- DNA sequences up and downstream of gene
Gene specific transcription factors (activate and repress)

Question 12

What is a nucleosome

Answer 12

Basic unit of eukaryotic chromosome structure
Segment of DNA wound around 8 histone proteins -form of chromatin
Histones- H2A, H2B, H3 & H4 x2
Assembles ~200bp
Many interactions between amino acids of histones and sugar phosphate backbone. Many amino acids residues are positively charged and DNA is negatively charged
High number of arginine and lysine amino acids which neutralise negative charge of DNA

Question 13

Histone modification

Answer 13

Epigenetics
Histone tails are subject to chemical modifications
These modifications also act as regulatory information

Question 14

Enzyme families modify the histone tails

Answer 14

Histone acetyl transferases- acetyl added onto histone tails
Histone de-acetylases- remove acetyl groups
I.e. histone acetylation (lysine residues)

Question 15

The environment can influence histone acetylation

Answer 15

Cell metabolism— histone acetyl transferases
Environmental factors and therapeutic drugs — enzyme inhibitors— histone deacetylases

Question 16

Nucleosome modifications

Answer 16

Involved in turning genes on or off
Respond to changes in environment inside and outside of cell
Epigenetic therapies can be used to treat some haematological cancers

Question 17

Dosage compensation

Answer 17

Need two copies of every gene to get right amount of protein
Sex determination:
Chromosomal differences between sexes, female XX, male XY
Y chromosome is small and gene poor
Dosage compensation equalises gene-expression levels
In female mammals- 1 of Xs is inactivated early in development balancing differences between males and females. X-inactivation is random, occurs in inner cell mass of blastocyst.
Inactive state is passed onto succeeding cell generations
X-inactivation is an example of a heritable epigenetic state

Question 18

Gene regulation and epigenetic mechanism summary

Answer 18

DNA is an inert carrier of info
It’s interpretation (gene expression) defines phenotype
Environmental effects can impact on gene activity
-gene specific transcription factors, epigenetic mechanisms (i.e. histone modifying enzymes )
X inactivation (random)
Long term chromosome silencing