Gene Expression - Oestrogen And Epigenetics

Question 1

What are trancription factors

Answer 1

Protein that controls the transcription of genes by binding to a specific region of DNA
ENsures genes are being expressed in correct cells
Allow organisms to respond to their environment

Question 2

Structure of a gene

Answer 2

Upstream = DNA before coding
Promoter = section of DNA upstream of the coding region that is the binding site for proteins that control the expression of the gene = RNA polymerase, transcription factors

Question 3

How do transcription factors work

Answer 3

1) Enter the nucleus from cytoplasm through nuclear pores
2) Transcription factors activated through signalling pathway
3) Transcription factor binds to promoter region of gene -> allowing or preventing transcription of gene
4) Transcription interacts with RNA polymerase to either bind RNA or preventing it from binding
5) Transcription factor either decreases or increases rate of transcription

Question 4

Oestrogen stimulation pathway

Answer 4

1) Oestrogen diffuses through the cell surface membrane into the cytoplasm
2) Oestrogen diffuses through a nuclear pore into the nucleus
3) Within the nucleus, oestrogen attaches to an ERα oestrogen receptor held within a protein complex, causing ERα oestrogen receptor to change shaoe
4) The new receptor shape allows it to detach from the protein complex and diffuse towards the gene being expressed
5) The receptor binds to a cofactor enabling it to bind to the promoter region of the gene and stimulates RNA polymerase binding and gene transcription

Question 5

How to answer gene expression questions

Answer 5

Clarify what is acting on the gene
And if its a stimulating or inhibiting effect
Effect this will have on mRNA produced -> more expression = more mRNA = more protein
Effect this has on the body

Question 6

What is epigenetics

Answer 6

Change in gene function without changes to the bases sequence of DNA

Question 7

What is the epigenome

Answer 7

Chemical modifications to histone proteins and DNA (except base changes) in an organism

Question 8

Describe histones

Answer 8

Histones are proteins
DNA in nucleus wrapped around histones
Chemically modified by adding acetyl or methyl groups without changing the base sequence, leading to the regulation of gene expression

Question 9

How are epigenomes different for different people

Answer 9

Heritable but environment causes changes
Smoking, stress, exercise
Internal signalling form bodys own cells can cause modifications to occur

Question 10

How are histones woundness controlled

Answer 10

-Chemical modification of histones and DNA controls how tightly its wounded
Intermolecular bonding between histones and DNA changes
-If DNA more tight, genes of these sections are switched off = promoter regions hidden from transcription factors and RNA polymerase
-Histones modification is reversible

Question 11

What is added during acetylation of histones

Answer 11

Acetyl groups (COCH3) added to lysine amino acids on histones

Question 12

How are histones acetylated

Answer 12

Lysine has positively charged R group = ionic bond with negatively charged phosphate backbone of DNA
Acetyl + lysine = removed positive ion, removes bond between histone and DNA so wrapped losely
Removal of acetyl returns lysine to positively charged state which has a stronger attraction to the DNA molecule inhibiting transcription

Question 13

Methylation of DNA

Answer 13

Methyl groups (CH3) added to a carbon molecule on cytosine and guanine bases
Suppresses transcription of affected gene
Methylated bases attract proteins to bind to DNA and inhibit transcription

Question 14

Inheriting epigenetic modiciations process naem

Answer 14

Epigenetic imprinting

Question 15

What is epigenetic imprinting

Answer 15

DNA methylation of certain genes and it occurs during the formation of oocytes and sperm cells

Question 16

WHat is Prader-Willi syndrome

Answer 16

Syndrome
Mother is carrier individuals that inherit the chromosome do not develop the disease
Father = inherit

Question 17

How do cancer treatments work

Answer 17

Drug taken
1) Removes methyl group from DNA of tumour suppressor genes = gene can be expressed
2) Proteins produced regulate cell cycle and stop tumour forming from cancer cells
3) Removes acetyl group from histone proteins attaches to oncogenes causes DNA to wrap tightly = silence genes
4) Reducing expression of oncogenes stops cancer cells, can programme cell death and stop replicating

Question 18

WHat is RNA interference

Answer 18

RNAi
Post-transcriptional modification occurs in cytoplasm
Sequence-specific silencing of gene expression
Very precise in silencing certain genes

Question 19

Describe small interfering RNA

Answer 19

Translation of mRNA inherited by RNAi
Small, double-stranded RNA = (siRNA)
Bind to mRNA that has been transcribed from target genes as their base sequence is complmentary
Attach to protein complex -> breakdown mRNA that has been transcribed from target genes -> cant be translated into proteins

Question 20

WHat are double stranded RNAs and what are they produced by

Answer 20

Double stranded RNA (dsRNA) produced by RNA-dependent RNa polymerases (RDRs)

Question 21

Describe the RNa interference pathway

Answer 21

1) dsRNA hydrolysed into smaller fragments forming siRNAs
2) siRNAs in the cytoplasm bind to protein complexes, using ATP to separate two strands of siRNA
3) Nucleotide bases exposed and pair with bases from mRNA
4) mRNA leaves nucleus, enters cytoplasm
5) siRNA binds to target mRNA through complementary base pairing
6) The mRNA cut into fragments by protein complex with the siRNA
7) Once cut cannot produce proteins

Question 22

How do siRNAs target mRNA

Answer 22

Complementary base pairing
Attachment of mRNA to siRNA localises mRNA to protien complex which carried out hydrolysis

Question 23

How do tumours harm the body

Answer 23

Damaging organs which tumour is located
Block or obstruct
Damage organs by exerting pressure

Question 24

Describe malignant tumours do

Answer 24

Cancerous
Grow rapidly, invade and destroy surrounding tissues
Cells in malignant tumour secrete chemicals that supply the tumour with nutrients, growth factors and oxygen from the blood stream
Metastasis = Cells can break off tumours and spread through bloodstream/ lymphatic system

Question 25

How are malignant tumours initiated by carcinogens

Answer 25

UV/ X-ray exposure Tobacco from cigarettes Asbestos Processed meat

Question 26

Describe benign tumours

Answer 26

Not cancerous Grow slowly Do not metastasise Can block or exert pressure in organs When removed dont grow back

Question 27

How can the formation of benign tumours be initiated

Answer 27

Inflammation or infection Injury Diet Genetics Toxins and radiation

Question 28

How are cancers formed

Answer 28

Expression of genes that control cell division changes Mutated gene is one that causes cancer = oncogenes Agents that cause cancer = carcinogens Uncontrollable cell division

Question 29

Tumour suppressor genes

Answer 29

Normal genes that code for proteins that regulate the cell cycle

Question 30

Describe the proteins that code for tumour suppressor genes

Answer 30

Function = DNA repair, slowing cell cycle, signal apoptosis (cell death) Ensure cells do not replicate if they contain mutated DNA Mutated or silenced

Question 31

What does hypermethylation of DNA

Answer 31

Causes transcription-inhibiting proteins to bind DNA Resullts in tumour development Over-addition of methyl groups to cytosine nucleotides

Question 32

What are proto-oncogenes

Answer 32

Normal genes that code for protiens that regulate cell growth and differentiation Oncogenes = mutated genes that cause cancer through deregulation of cell growth Cause proteins that stimulate cell growth and division to be constantly activated Cell cycle sped up

Question 33

What do proto-oncogene mutations result in

Answer 33

Mutations occur through inversion or translocation mutations when activating gene segments Gene expression upregulated or Protein produced being constantly activated (cant switch off)

Question 34

How metastatic cancer develops

Answer 34

1) Oncogenes arise due to carcinogens 2) Cancerous cell does not respond to signals from other cells so continues to divide 3) Mitosis 4) Cancerous cels not removed by immune system 5) rapid mitosis 6) Tumour gets bigger 7) tumour supplies with blood and lumph vessels, if malignant tumour, tumour cells spread in blood and lymph to other parts of the body 8) Metastasis. Tumour cells invade other tissues forming secondary tumours throughout the body

Question 35

How does increased oestrogen concentrations in the development of some breast cancers

Answer 35

Oestrogen stimulates ERα oestrogen receptor High conc = over expression of oestrogen gene or from oestrogen taken in medication Form oestrogen dependent breast tumours, need oestrogen to stimulate cell cycle genes Cancer cells have oestrogen receptros that promote cell growth Genes switches on trhoguh oestrogen dependent gene expression pathway in which oestrogen diffuses into the cell and through a nuclear pore until it reaches the oestrogen recepeotrs

Question 36

How do alterations to tumour suppressor genes lead to tumours

Answer 36

1) Increased methylation of tumour suppressor genes 2) Mutation in tumour suppressor genes 3) Tumour suppressor genes not transcribes 4) Amino acid sequence altered 5) Rapid and uncontrollable cell division

Question 37

What are the effects of having a non-functional form of an enzyme

Answer 37

1) Enzyme doesnt bind to broken DNA 2) DNA not repaired still broken 3) cell division forms tumour 4) Tumour suppressor genes not effective 5) May have no effect in diploid 6) Still have a functional enzyme gene

Question 38

What is epigenetics 2 marker

Answer 38

Heritable changes in gene function Without changes to the base sequence of DNA

Question 39

How does methylation form cancers

Answer 39

Methyl groups added to tumour suppressor gene Transcription of tumour suppressor genes inhibited Leading to uncontrollable cell division

Question 40

How does methylation form cancers

Answer 40

Methyl groups added to tumour suppressor gene Protein not produced that prevents cell division and that causes cell death Transcription of tumour suppressor genes inhibited Leading to uncontrollable cell division

Question 41

How does a protein stimulate gene expression

Answer 41

1) Protein is a transcription factor 2) Binds to a promoter 3) stimulates RNA polymerase

Question 42

SUT1 produces sense mRNA, genetically modified version produces sense mRNA How does the production of antisense SUT1 mRNA reduce expression of SUT1 gene

Answer 42

Antisense mRNA complementary to sense mRNA Antisense mRNA binds to mRNA Ribosomes cant bind Preventing translation of mRNA

Question 43

What does a decrase in acetylation cause

Answer 43

Decrease in aetylation i nhostones Increase positive charge of histones Increases strength of association between DNA and histones Transcription factors cannot access DNA and bind to the promoter No transcription and mRNA production

Question 44

What does an increase in methylation cause

Answer 44

Decrease in acetylation Transcription factors cant bind No transcription and mRNA produced

Question 45

How do transcription factors control gene expression

Answer 45

Protein binds to specific promoter, ensuring correct specific genes are expressed due to complementary shapes of the promoter and transcription factors Example = oestrogen

Question 46

How does the oestrogen stimulation pathway work

Answer 46

Oestrogen diffuses through the plasma membrane intot he cytoplasm Oestrogen diffuses through a nuclear pore into the nucleus Oestrogen attaches to an oestrogen receptor that is held within a protein complex, causing ERa oestrogen receptro to change shape This new shape of the oestrogen receptor allows it to detach from the protein complex and diffuse towards the gene to be expressed The ERa oestrogen receptor binds to a cofactor which enables it to bind to the promoter region of the gene, stimulating RNA polymerase binding and gene transcription to begin

Question 47

How does gene expression not get activated

Answer 47

Transcription factor binds to promoter But some transcription factors bind and cause inhibition of transcription Prevetnign RNA polymerase binding and beginning transcription

Question 48

How is gene expresion controled by translation

Answer 48

Transcription to gene occurs producing mRNA MRNA becomes double stranded DICER enzyme cuts the double stranded mRNA into siRNAs Each siRNA binds to a protein complex SiRNA becomes single stranded siRNA binds to complementary mRNA siRNA binds to mRNA, breaks it into sections then binds to another mRNA strand Destroys mRNA so it cannot be used in translation