20 Gene expression Flashcards
what needs to happen for transcription to happen
the gene is switched on by transcriptional factors
what are transcriptional factors
molecules that move form the cytoplasm to the nucleus
what do transcriptional factors do
- has a site that binds to a specific base sequence of DNA in the nucleus
- when it binds it causes that region of DNA to begin the process of transcription
what is the process of transcription
- messenger RNA (mRNA) is produced and the information it carries is translated into a polypeptide
what happens if a gene is not being expressed
- the site on the transcriptional, factor that binds to DNA is not active
- as the site on the transcriptional factor binding to DNA is not active it cannot cause transcription and polypeptide synthesis
how do hormones affect gene transcription
can switch on a gene and start transcription by combining with a receptor site in the transcriptional factor
how does oestrogen affect gene transcription
- Oestrogen is a lipid soluble molecule that diffuses through the phospholipid portion of the cell surface membrane
2.once inside the cytoplasm oestrogen binds with a site on a receptor molecule of transcriptional factors. the shape of this site and the the shape of the oestrogen molecule are complementary - by binding with the site oestrogen changes the shape of the DNA binding site on the transcription factor which can now bind to DNA
- the transcriptional factor can now enter the nucleus through a nuclear pore and binds to a specific base sequence on DNA
- the combination of transcriptional factors with DNA stimulates transcription of the gene that makes up that portion of DNA
what is epigenetic
- provides an explanation as to how environmental influences such as diet and stress can subtly alter the genetic inheritance of an organism offsprings without changing the DNA sequence
what are epigenomes
- chemical tags that forms a second layer on DNA and histones
- determines the shape of the DNA- histone complex
what is epigenetic silencing
- keeps genes that are inactive in a tightly packed arrangement ensuring that they cannot be read
effects of a the flexible epigenome
- factors like diet and stress can cause the chemical tags to adjust the wrapping and unwrapping of the DNA so switches genes on and off
what is the epigenome of a cell
the accumulation of the signal it has received in its lifetime so acts like a cellular memory
what happens when the association of histone with DNA is weak
- the DNA histone complex is less condensed and the DNA is accessible to transcription factors which can initiate the production of mRNA switching the gene on
what happens when the association of histone with DNA is strong
- the DNA histone complex is more condensed and the DNA is not accessible to transcription factors which cannot initiate the production of mRNA so the gene is switched off
what is acetylation
the process where an acetyl group is transferred to a molecule of DNA
what is deacetylation
the reverse reaction where the acetyl group is removed from the molecule of histone
effects of decreased acetylation
- increases the positive charge on histone increasing their attraction to the phosphate group of DNA
- the association between DNA and histone is stronger and the DNA is not accessible to transcription factors
what is methylation
the addition of a methyl group (CH3) to a molecule (cytosine in DNA)
effects of methylation
inhibits the transcription of genes by
1. preventing the binding of transcription factors to DNA
2. attracts proteins that condense the DNA - Histone complex making the DNA inaccessible to transcription factors
examples of epigentics and inheritiance
- experiments on rats have shown that female offspring who received good care when young respond better to stress in later life and nurture their young better
- good maternal behaviour in rats transmit epigentic information unto their offspring DNA without passing through the egg or sperm - in humans when a mum has gestational diabetes the fetus is exposed to high concentration of glucose
- these high glucose concentrations cause epigenetic changes in the daughters DNA increasing the likelihood that she will develop gestational diabetes
how can epigentic cause disease
- altering any of the epigenetic process can cause abnormal activation or silencing of genes
1. there are specific sections of DNA that have no methylation in normal cells but in cancer cells these genes become highly methylated causing genes that should be active to be switched off
2. some active genes help repair DNA so prevent cancer - in people with inherited cancer, increased methylation of these genes has led to these proactive genes being switched off so damaged base sequences in DNA are not repaired leading to cancer
how is disease treated with epigenetic
- epigentic treatments use drugs to inhibit certain enzymes involving histone acetylation or DNA methylation
- drugs that inhibit enzymes that cause DNA methlaylation can reactivate genes that have been silences
- epigentic therapy must be specifically targeted in cancer cells, if the drugs were to affect normal cell that could activate gene transcription making them cancerous - diagnostic tests have been developed to detect early stages for cancer
- these tests identify levels of DNA methylation and histone acetylation at early stages so patients can seek early treatment
what is the effect of DNA interference on gene expression
- the translation if mRNA produced by the gene can be inhibited by breaking mRNA down before its coded information can be translated in a polypeptide
1. an enzyme cuts large double stranded molecules of RNA into smaller sections (small interfering RNA - siRNA)
2. one of the siRNA strands combine with a new enzyme
3. siRNA molecules guides the enzyme to a messenger RNA molecules by pairing up its bases with the complementary ones on the section of the mRNA molecule
4. once in position the enzyme cuts the mRNA into smaller section
5. the mRNA is no longer capable of being translated into a polypeptide
6. this means that the gene had not been expressed and had been blacked
what is cancer
- a group of disease caused by damage to the genes that regulate mitosis and the cell cycle
- leads to unrestricted growth of cells resulting in a tumor
what are malignant tumor
cancerous
what are benign cancers
non cancerous
features of a benign tumour
- can be large
- grows slowly
- normal sized nucleus
- cells are well differentiated
- remain in the tissue in which they arise
- can be removed by surgery alone
features of a malignant tumour
- can be large
- grows rapidly
larger and darker nucleus - cells become de differentiated
- spread (metastasis)
- treated with chemo or radiotherapy
what is a proto - oncogenes
- stimulates a cell to divide when growth factors attach to a protein receptor on its cell surface membrane
- this activates genes that cause DNA to replicate and cell to divide
what is an oncogene
- mutations of proto - oncogene
why are oncogenes permanently activated
- receptor protein on the cell surface membrane can be permanently activated so that cell division is switched on even in the absence of growth substances
- the oncogene may code for a growth factor that is then produced in excessive amounts stimulating excessive cell growth
what are tumour suppressor genes
- slow down cell division
- repair mistakes in DNA
- tell the cell when to apoptosis
what happens if a tumour becomes mutated
- it is inactivated
- so stops inhibiting cell division
- so cells grow out of control forming tumours
how does hypermethylation lead to canver
- occurs in the promoter region of the tumour suppressor genes
- this leads to the tumour suppressor gene being inactivated
- transcription of the promoter regions of tumour suppressor gene is inhibited
- tumour suppressor gene is silenced
- inactivation of tumour suppressor leads to increased cell division and the formation if a tumour
how does hypomethylation lead to cancer
- occurs in oncogenes where it leads to their activation and the formation if tumours
how is oestrogen concentration linked to breast father
- after menopause a woman’s risk of developing breast cancer increase due to increased levels of oestrogen
- fat cells of breast produces more oestrogen after menopause
- once a tumour has developed, it further increases oestrogen concentration which increases the development of the tumour
- oestrogen activates a gene by binding to a receptor which promotes transcription
- if the gene that oestrogen acts on is one that controls cell division and growth, then it will be activated and it s continued growth could cause a tumour
- oestrogen causes proto - oncogenes of cells in breast tissue to develop into oncogene leading to the development of a tumour
