Gene Expression - Oestrogen And Epigenetics Flashcards
What are trancription factors
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
Structure of a gene
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
How do transcription factors work
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
Oestrogen stimulation pathway
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
How to answer gene expression questions
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
What is epigenetics
Change in gene function without changes to the bases sequence of DNA
What is the epigenome
Chemical modifications to histone proteins and DNA (except base changes) in an organism
Describe histones
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
How are epigenomes different for different people
Heritable but environment causes changes
Smoking, stress, exercise
Internal signalling form bodys own cells can cause modifications to occur
How are histones woundness controlled
-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
What is added during acetylation of histones
Acetyl groups (COCH3) added to lysine amino acids on histones
How are histones acetylated
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
Methylation of DNA
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
Inheriting epigenetic modiciations process naem
Epigenetic imprinting
What is epigenetic imprinting
DNA methylation of certain genes and it occurs during the formation of oocytes and sperm cells
WHat is Prader-Willi syndrome
Syndrome
Mother is carrier individuals that inherit the chromosome do not develop the disease
Father = inherit
How do cancer treatments work
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
WHat is RNA interference
RNAi
Post-transcriptional modification occurs in cytoplasm
Sequence-specific silencing of gene expression
Very precise in silencing certain genes
Describe small interfering RNA
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
WHat are double stranded RNAs and what are they produced by
Double stranded RNA (dsRNA) produced by RNA-dependent RNa polymerases (RDRs)
Describe the RNa interference pathway
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
How do siRNAs target mRNA
Complementary base pairing
Attachment of mRNA to siRNA localises mRNA to protien complex which carried out hydrolysis
How do tumours harm the body
Damaging organs which tumour is located
Block or obstruct
Damage organs by exerting pressure
Describe malignant tumours do
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
How are malignant tumours initiated by carcinogens
UV/ X-ray exposure
Tobacco from cigarettes
Asbestos
Processed meat
Describe benign tumours
Not cancerous
Grow slowly
Do not metastasise
Can block or exert pressure in organs
When removed dont grow back
How can the formation of benign tumours be initiated
Inflammation or infection
Injury
Diet
Genetics
Toxins and radiation
How are cancers formed
Expression of genes that control cell division changes
Mutated gene is one that causes cancer = oncogenes
Agents that cause cancer = carcinogens
Uncontrollable cell division
Tumour suppressor genes
Normal genes that code for proteins that regulate the cell cycle
Describe the proteins that code for tumour suppressor genes
Function = DNA repair, slowing cell cycle, signal apoptosis (cell death)
Ensure cells do not replicate if they contain mutated DNA
Mutated or silenced
What does hypermethylation of DNA
Causes transcription-inhibiting proteins to bind DNA
Resullts in tumour development
Over-addition of methyl groups to cytosine nucleotides
What are proto-oncogenes
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
What do proto-oncogene mutations result in
Mutations occur through inversion or translocation mutations when activating gene segments
Gene expression upregulated or
Protein produced being constantly activated (cant switch off)
How metastatic cancer develops
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
How does increased oestrogen concentrations in the development of some breast cancers
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
How do alterations to tumour suppressor genes lead to tumours
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
What are the effects of having a non-functional form of an enzyme
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
What is epigenetics 2 marker
Heritable changes in gene function
Without changes to the base sequence of DNA
How does methylation form cancers
Methyl groups added to tumour suppressor gene
Transcription of tumour suppressor genes inhibited
Leading to uncontrollable cell division
How does methylation form cancers
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
How does a protein stimulate gene expression
1) Protein is a transcription factor
2) Binds to a promoter
3) stimulates RNA polymerase
SUT1 produces sense mRNA, genetically modified version produces sense mRNA
How does the production of antisense SUT1 mRNA reduce expression of SUT1 gene
Antisense mRNA complementary to sense mRNA
Antisense mRNA binds to mRNA
Ribosomes cant bind
Preventing translation of mRNA
What does a decrase in acetylation cause
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
What does an increase in methylation cause
Decrease in acetylation
Transcription factors cant bind
No transcription and mRNA produced
How do transcription factors control gene expression
Protein binds to specific promoter, ensuring correct specific genes are expressed due to complementary shapes of the promoter and transcription factors
Example = oestrogen
How does the oestrogen stimulation pathway work
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
How does gene expression not get activated
Transcription factor binds to promoter
But some transcription factors bind and cause inhibition of transcription
Prevetnign RNA polymerase binding and beginning transcription
How is gene expresion controled by translation
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
