Environmental Effects and Epigenetics

Question 1

define phenotype

Answer 1

the set of observable characteristics of an individual. It is due to the interaction of their genotype with the environment (toxins, diets etc.)

Question 2

give an example of how genetics and environment interact to form the phenotype

Answer 2

Example: Monozygotic twins have the same genotype (due to split of one zygote) but can be usually told apart by subtle difference. These differences are due to environmental factors.

Question 3

what are housekeeping genes? (should know by now)

Answer 3

set of structural genes constitutively expressed in all cell types (essential for life) e.g. genes that code for proteins such as RNA polymerase, pyruvate kinase, histones etc.

Question 4

what causes a cell to be specialised and have a different function from other cells?

Answer 4

Cell identity is determined by the expression of cell-specific genes - genes that are not switched on in every cell and produce proteins that allow a cell to carry out its specialised function:
E.g. a cell specific gene that is turned on in skeletal muscle is troponin. It is required by muscle to carry out its function of contraction.

Question 5

explain epigenetics

Answer 5

• Epigenetics involves changes in gene expression without alteration to genetic code
• Is characterised as an environmental mechanism.
• Epigenetic processes generate multiple phenotypes from same genotype
• Epigenetics allows differentiated cells to maintain their pattern of gene expression throughout their life.

Question 6

what regulates gene expression?

Answer 6

1. Transcriptional Control: The most important step on determining a cell type (deciding what proteins are produced)
2. RNA Processing Control: Splicing (introns removed)
3. RNA Transport: This is an active transport process that requires ATP
4. Translation Control: If mRNA is degraded the protein will not be generated
5. mRNA degradation control: control whether or not mRNA should be degraded at this stage
6. Protein activity control: Protein can generate in active form then inactivated or generated in an inactive form then activated.

Question 7

define genes

Answer 7

transcriptional units composed of:
structural information- which code for a protein
regulatory sequences- which give instructions for expression (will mRNA be produced or not).

Question 8

what are 2 epigenetic examples of regulating gene expression?

Answer 8

TATA box
Enhancers

Question 9

explain the TATA box example in regulating gene expression?

Answer 9

• Upstream, immediately adjacent to the coding region there is 5’ regulatory sequence called the TATA box. It is a gene promoter region.
• Gene transcription factors (GTF) (proteins) are recruited by a gene to bind to its 5’ promoter region and recruit RNA polymerase II to initiate transcription,
• They indicate where the gene starts - RNA polymerase cannot recognise transcription start sites on its own
• They are located on around 50% of known genes.

Question 10

what do GTFs allow?

Answer 10

for a low basal level of transcription

Question 11

what are enhancers?

Answer 11

DNA sequences up & downstream of a gene which recruit transcription factor (gene regulatory proteins) to bind to them.

Question 12

explain the enhancer example in regulating gene expression?

Answer 12

The bound transcription factors then decide whether RNA polymerase is active or inactive so then determine whether mRNA will be produced or not i.e is a gene active or not.
Often these transcription factors respond to environmental signals & stress e.g. Hormones, Nutritional signals etc.

Question 13

define allele

Answer 13

Different versions of the same gene

Question 14

what is a nucleosome?

Answer 14

A globular ball of protein with a total of 140bp of DNA wrapped around it twice
Nucleosomes contains 8 histones (histone octamer) – 2x H2A, H2B, H3 & H4
Nucleosomes appear every 200 bp so you have a naked zone approx. 60 bp long
Many interactions between amino acids of histones and sugar phosphate backbone
High number of arginine and lysine amino acids which neutralise the negative charge of the DNA

Question 15

explain histone modification

Answer 15

Histone tails are made of chains of amino acids that have chemical tags on them.
The addition of these tags are catalysed by enzymes, (post translation after AA sequence is produced)
Examples of tags are Acetyl, Methyl tags.
Tails highly conserved- suggests single mutation to sequence will result in death of cell

Question 16

what is the histone code?

Answer 16

The histone code (the chemical modification of tails) on nucleosomes carry information determining when genes attached to them should be on or off - epigenetic mechanism

Question 17

what modifies histone tails?

Answer 17

Enzyme families modify the histone tails i.e. one enzyme adds tags and one removes them
So gene activity is determined by the level of enzymes e.g. more HATS means more acetylation, more HD means less acetylation

Question 18

how does environmental factors effect histone modification?

Answer 18

Things in the environment can determine the enzyme activity e.g. factors in our diet can inhibit enzymes so ultimately determine whether tails are acetylated or not acetylated and so whether genes are turned on or off (epigenetic mechanism)

Question 19

what does acetylation do?

Answer 19

Acetylation: open conformation of chromatin as acetylated histones cannot pack as closely together, means transcription factors can bind to enhancers and RNA polymerase has access to gene.

Question 20

what is epigenetic therapy

Answer 20

Gene activity can be modified by producing drugs that modifying enzymes that target histone tails

Question 21

what can epigenetic therapy be used to treat?

Answer 21

can be used to treat some haematological cancers

Question 22

what do nucleosome modification determine?

Answer 22

• involved in turning genes on or off
• Respond to changes in environment inside and outside of the cell.

Question 23

what sex chromosomes do M & F carry?

Answer 23

Females have two X chromosomes
Males have one X and one small gene-poor Y

Question 24

what is dosage compensation?

Answer 24

• For any gene we have two copies
• The number of genes determines the level of expression of said gene e.g. if you had three copies of each gene you would 1.5 X more protein and 1.5 X more mRNA.
• Males only have one copy of each gene on the X chromosome whereas females have two copies of each gene (two X chromosomes) – so why is there not an issue??
• Biology has overcome this.
• Dosage compensation equalises the amount of gene product that comes whether you have one or two copies of the X chromosome.

Question 25

how is dosage compensation done in mammals?

Answer 25

one of the X chromosomes in females in inactivated (condensed and silenced – in early development) so male and female have one genetically activated X chromosome.
Inactive X chromosome is visible in eukaryotic cell nucleus. It is called the bar body.
X-inactivation is random, in women either the paternal or maternal is inactivated.
This occurs in early development during the blastocyst stage (very early) – some cells will inactivate paternal and other will inactivate the maternal. All cells derived from these will have the same inactivated X chromosome.
X-inactivation is an example of heritable epigenetic state – passed on to daughter cells.

Question 26

how is dosage compensation done in fruit flies?

Answer 26

in males all the genes on the X chromosomes are upregulated - extra active genes so that balances out the two copies of each gene within the female.